{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRTN3 serves as a versatile regulator of endoplasmic reticulum (ER) structure and trafficking. It functions as a selective autophagy receptor for the degradation of ER tubules by oligomerizing and engaging LC3-interacting regions, thereby mediating ER‐phagy (1:."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, RTN3 promotes the establishment of ER–plasma membrane contact sites that are critical for nonclathrin endocytosis of receptors such as EGFR (2:"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", and it alters early secretory pathway dynamics by modulating ER–Golgi protein trafficking (3:."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " RTN3 also contributes to cellular proteostasis by facilitating the clearance of misfolded or mutant prohormone aggregates via ER‐coupled autophagy (4:"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", and it organizes ER–endosome membrane contact sites to support endosome maturation (5:."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, by associating with VLDL core proteins in ER‐derived vesicles, RTN3 regulates the ER-to-Golgi transport of nascent lipoproteins (6:"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", and recent work has underscored its collaborative role with other reticulophagy receptors (e.g. ATL3 and CALCOCO1) in preserving ER proteostasis (7:."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the nervous system, RTN3 plays a multifaceted role in modulating protein processing and neuronal integrity. By directly interacting with beta‐secretase (BACE1), RTN3 negatively regulates its activity hence reducing amyloidogenic processing of APP, with RTN3 deficiency resulting in increased BACE1 levels and amyloid deposition (8:."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " It is also up‐regulated under ER stress to influence the anti‐apoptotic activity of Bcl‑2 in neurons (9:"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", and its multiple isoforms are dynamically expressed in the developing and mature brain to support neuronal survival and plasticity (10:"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "; 11:."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Structural determinants such as a conserved C‑terminal QID triplet and an omega‐shaped membrane topology are crucial for RTN3’s binding to BACE1 (12:"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "; 13:"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ", and comparative studies indicate that, unlike its homolog RTN1, RTN3 plays a more prominent role in Alzheimer pathology (14:."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Furthermore, RTN3’s involvement in lipid metabolism in the brain (15:"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": ", the formation of dystrophic neurites and subsequent impairments in dendritic spine density (16:"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": ", and in promoting neurite outgrowth via VAMP7‐dependent secretion (17:"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": "highlight its diverse roles in neurons. In addition, genetic variants of RTN3 have been reported to perturb axonal transport of BACE1 (18:"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": ", and its direct association with BACE1 is central to reducing β‑amyloid peptide generation (19:"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": "; 20:."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": " In transgenic murine models, modest increases in RTN3 expression have been shown to suppress amyloidogenic processing and reduce plaque burden (21:"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": "; 22:"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": ", while its regulatory interplay with CXCR4 further implicates RTN3 in modulating neuronal migration (23:."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": " Notably, inducible RTN3 aggregation in the hippocampus correlates with deficits in learning and memory (24:."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond the central nervous system, RTN3 is involved in a broad array of cellular stress responses, apoptosis, and host–pathogen interactions. It participates in apoptotic pathways by interacting with partners such as CRELD1 and FADD, thereby modulating the subcellular distribution of Bcl‑2 and triggering caspase cascades upon ER stress (25:"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "25"}]}, {"type": "t", "text": "; 26:"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "26"}]}, {"type": "t", "text": "; 27:"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "27"}]}, {"type": "t", "text": "; 28:."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "28"}]}, {"type": "t", "text": " Its role in modulating apoptosis may also link RTN3 to vascular cell apoptosis and atherosclerotic processes (29:"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "29"}]}, {"type": "t", "text": "; 31:"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "30"}]}, {"type": "t", "text": "; 32:."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "31"}]}, {"type": "t", "text": " Although common RTN3 genetic variants do not appear to affect platelet beta-secretase activity (33:"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "32"}]}, {"type": "t", "text": ", overexpression of its homolog HAP (identical to RTN3) can induce apoptosis through ER Ca²⁺ depletion (34:."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "33"}]}, {"type": "t", "text": " In the kidney, reduced RTN3 expression exacerbates injury and fibrosis, likely via disruptions in mitochondrial function and ER–mitochondrion contacts (35:"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "34"}]}, {"type": "t", "text": "; 40:."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "35"}]}, {"type": "t", "text": " RTN3 also modulates viral replication: it restricts hepatitis C virus propagation by interfering with viral protein interactions (36:"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "36"}]}, {"type": "t", "text": ", influences enterovirus 71 RNA synthesis (37:"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "37"}]}, {"type": "t", "text": ", and is required for the formation of SARS‑CoV‑2 replication organelles in cooperation with RTN4 (38:"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "38"}]}, {"type": "t", "text": "; 39:."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "39"}]}, {"type": "t", "text": " Collectively, these findings underscore RTN3’s importance as an integrative regulator of cellular homeostasis, stress responses, and host defense mechanisms (30:"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "40"}]}, {"type": "t", "text": "; 41:."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Paolo Grumati, Giulio Morozzi, Soraya Hölper, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Full length RTN3 regulates turnover of tubular endoplasmic reticulum via selective autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.25555"}], "href": "https://doi.org/10.7554/eLife.25555"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28617241"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28617241"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Giusi Caldieri, Elisa Barbieri, Gilda Nappo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reticulon 3-dependent ER-PM contact sites control EGFR nonclathrin endocytosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.aah6152"}], "href": "https://doi.org/10.1126/science.aah6152"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28495747"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28495747"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yuichi Wakana, Satoshi Koyama, Ken-ichi Nakajima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reticulon 3 is involved in membrane trafficking between the endoplasmic reticulum and Golgi."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2005.07.012"}], "href": "https://doi.org/10.1016/j.bbrc.2005.07.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16054885"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16054885"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Corey N Cunningham, Jeffrey M Williams, Jeffrey Knupp, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cells Deploy a Two-Pronged Strategy to Rectify Misfolded Proinsulin Aggregates."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2019.05.011"}], "href": "https://doi.org/10.1016/j.molcel.2019.05.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31176671"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31176671"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Haoxi Wu, Gia K Voeltz "}, {"type": "b", "children": [{"type": "t", "text": "Reticulon-3 Promotes Endosome Maturation at ER Membrane Contact Sites."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2020.12.014"}], "href": "https://doi.org/10.1016/j.devcel.2020.12.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33434526"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33434526"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Shaila Siddiqi, Olga Zhelyabovska, Shadab A Siddiqi "}, {"type": "b", "children": [{"type": "t", "text": "Reticulon 3 regulates very low density lipoprotein secretion by controlling very low density lipoprotein transport vesicle biogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Can J Physiol Pharmacol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1139/cjpp-2018-0077"}], "href": "https://doi.org/10.1139/cjpp-2018-0077"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29756473"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29756473"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Kamal Kumar, Ravi Chidambaram, Smriti Parashar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RTN3L and CALCOCO1 function in parallel to maintain proteostasis in the endoplasmic reticulum."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autophagy (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15548627.2024.2353502"}], "href": "https://doi.org/10.1080/15548627.2024.2353502"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38818751"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38818751"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Qi Shi, Yingying Ge, Md Golam Sharoar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impact of RTN3 deficiency on expression of BACE1 and amyloid deposition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.1588-14.2014"}], "href": "https://doi.org/10.1523/JNEUROSCI.1588-14.2014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25319692"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25319692"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Qingwen Wan, Ersheng Kuang, Wei Dong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reticulon 3 mediates Bcl-2 accumulation in mitochondria in response to endoplasmic reticulum stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Apoptosis (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10495-006-0574-y"}], "href": "https://doi.org/10.1007/s10495-006-0574-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17191123"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17191123"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Franck Di Scala, Luc Dupuis, Christian Gaiddon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tissue specificity and regulation of the N-terminal diversity of reticulon 3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20040458"}], "href": "https://doi.org/10.1042/BJ20040458"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15350194"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15350194"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Bing Qi, Yipeng Qi, Akihiro Watari, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pro-apoptotic ASY/Nogo-B protein associates with ASYIP."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.10297"}], "href": "https://doi.org/10.1002/jcp.10297"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12811824"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12811824"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Wanxia He, Xiangyou Hu, Qi Shi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mapping of interaction domains mediating binding between BACE1 and RTN/Nogo proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2006.07.094"}], "href": "https://doi.org/10.1016/j.jmb.2006.07.094"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16979658"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16979658"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Wanxia He, Qi Shi, Xiangyou Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The membrane topology of RTN3 and its effect on binding of RTN3 to BACE1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M704181200"}], "href": "https://doi.org/10.1074/jbc.M704181200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17699523"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17699523"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Qi Shi, Yingying Ge, Wanxia He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RTN1 and RTN3 protein are differentially associated with senile plaques in Alzheimer's brains."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-017-05504-9"}], "href": "https://doi.org/10.1038/s41598-017-05504-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28733667"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28733667"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Rong Xiang, Liang-Liang Fan, Hao Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased Reticulon 3 (RTN3) Leads to Obesity and Hypertriglyceridemia by Interacting With Heat Shock Protein Family A (Hsp70) Member 5 (HSPA5)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circulation (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCULATIONAHA.117.030718"}], "href": "https://doi.org/10.1161/CIRCULATIONAHA.117.030718"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29716941"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29716941"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Qi Shi, Xiangyou Hu, Marguerite Prior, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The occurrence of aging-dependent reticulon 3 immunoreactive dystrophic neurites decreases cognitive function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.5887-08.2009"}], "href": "https://doi.org/10.1523/JNEUROSCI.5887-08.2009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19386906"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19386906"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "José Wojnacki, Sébastien Nola, Philippe Bun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of VAMP7-Dependent Secretion of Reticulon 3 in Neurite Growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2020.108536"}], "href": "https://doi.org/10.1016/j.celrep.2020.108536"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33357422"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33357422"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Yongyi Zou, Wanxia He, Kangli Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of rare RTN3 variants in Alzheimer's disease in Han Chinese."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00439-018-1868-1"}], "href": "https://doi.org/10.1007/s00439-018-1868-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29356939"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29356939"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "H Kume, Y Konishi, K S Murayama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of reticulon 3 in Alzheimer's disease brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropathol Appl Neurobiol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2990.2008.00974.x"}], "href": "https://doi.org/10.1111/j.1365-2990.2008.00974.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19284479"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19284479"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Lei Zhu, Rong Xiang, Wei Dong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Anti-apoptotic activity of Bcl-2 is enhanced by its interaction with RTN3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Biol Int (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellbi.2007.01.032"}], "href": "https://doi.org/10.1016/j.cellbi.2007.01.032"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17379544"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17379544"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Wataru Araki, Akiko Oda, Kazumi Motoki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reduction of β-amyloid accumulation by reticulon 3 in transgenic mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Alzheimer Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2174/1567205011310020003"}], "href": "https://doi.org/10.2174/1567205011310020003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22742855"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22742855"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Jonathon E Heath, Sandra L Siedlak, Xiongwei Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Widespread distribution of reticulon-3 in various neurodegenerative diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropathology (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1440-1789.2010.01107.x"}], "href": "https://doi.org/10.1111/j.1440-1789.2010.01107.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20374499"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20374499"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Haitao Li, Rong Liang, Yanan Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RTN3 Regulates the Expression Level of Chemokine Receptor CXCR4 and is Required for Migration of Primordial Germ Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms17040382"}], "href": "https://doi.org/10.3390/ijms17040382"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27070582"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27070582"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Qi Shi, Marguerite Prior, Xiangdong Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Preventing formation of reticulon 3 immunoreactive dystrophic neurites improves cognitive function in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.2445-12.2013"}], "href": "https://doi.org/10.1523/JNEUROSCI.2445-12.2013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23407961"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23407961"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Rong Xiang, Shuiping Zhao "}, {"type": "b", "children": [{"type": "t", "text": "RTN3 inducing apoptosis is modulated by an adhesion protein CRELD1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biochem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11010-009-0163-9"}], "href": "https://doi.org/10.1007/s11010-009-0163-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19521671"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19521671"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Hideaki Kume, Kiyoko S Murayama, Wataru Araki "}, {"type": "b", "children": [{"type": "t", "text": "The two-hydrophobic domain tertiary structure of reticulon proteins is critical for modulation of beta-secretase BACE1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jnr.22112"}], "href": "https://doi.org/10.1002/jnr.22112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19405102"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19405102"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Ziwei Yang, Jun Wang, Bailin He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RTN3 inhibits RIG-I-mediated antiviral responses by impairing TRIM25-mediated K63-linked polyubiquitination."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.68958"}], "href": "https://doi.org/10.7554/eLife.68958"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34313226"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34313226"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Rong Xiang, Yingle Liu, Lei Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adaptor FADD is recruited by RTN3/HAP in ER-bound signaling complexes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Apoptosis (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10495-006-0082-0"}], "href": "https://doi.org/10.1007/s10495-006-0082-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17031492"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17031492"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Yaqin Chen, Shuiping Zhao, Rong Xiang "}, {"type": "b", "children": [{"type": "t", "text": "RTN3 and RTN4: Candidate modulators in vascular cell apoptosis and atherosclerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.22838"}], "href": "https://doi.org/10.1002/jcb.22838"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20717916"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20717916"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Jingxian Liu, Wanlong Zhu, Haina Qin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NMR studies reveal a novel mode for hFADD to bind with the unstructured hRTN3 which initiates the ER-stress activated apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2009.04.024"}], "href": "https://doi.org/10.1016/j.bbrc.2009.04.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19364499"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19364499"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Yaqin Chen, Rong Xiang, Shuiping Zhao "}, {"type": "b", "children": [{"type": "t", "text": "The potential role of RTN3 in monocyte recruitment and atherosclerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biochem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11010-011-1089-6"}], "href": "https://doi.org/10.1007/s11010-011-1089-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21964562"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21964562"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Robyn Carson, Amy Jayne McKnight, Stephen Todd, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Variation in RTN3 and PPIL2 genes does not influence platelet membrane beta-secretase activity or susceptibility to alzheimer's disease in the northern Irish population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuromolecular Med (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12017-009-8080-3"}], "href": "https://doi.org/10.1007/s12017-009-8080-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19669607"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19669607"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Hua Xu, Qing Zhou, Xin Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Co-involvement of the mitochondria and endoplasmic reticulum in cell death induced by the novel ER-targeted protein HAP."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Biol Lett (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2478/s11658-006-0019-1"}], "href": "https://doi.org/10.2478/s11658-006-0019-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16847569"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16847569"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Liang-Liang Fan, Ran Du, Ji-Shi Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of RTN3 phenocopies chronic kidney disease and results in activation of the IGF2-JAK2 pathway in proximal tubular epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Mol Med (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s12276-022-00763-7"}], "href": "https://doi.org/10.1038/s12276-022-00763-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35596061"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35596061"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Ran Du, Ji-Shi Liu, Hao Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RTN3 deficiency exacerbates cisplatin-induced acute kidney injury through the disruption of mitochondrial stability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mitochondrion (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mito.2024.101851"}], "href": "https://doi.org/10.1016/j.mito.2024.101851"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38336146"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38336146"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Chih-Lang Lin, Rong-Nan Chien, Kung-Hao Liang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Intrahepatic HCV RNA Level and Genotype 1 Independently Associate with Hepatic Reticulon 3 Expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Anticancer Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.21873/anticanres.11641"}], "href": "https://doi.org/10.21873/anticanres.11641"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28551625"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28551625"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Li Li, Haiyan Zhong, Mao Fan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Molecular Mechanism of Action of hnRNP K and RTN3 in the Replication of Enterovirus 71]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bing Du Xue Bao (2015)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26164948"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26164948"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Miao Gan, Yipeng Qi, Qingwen Wan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mammalian apoptosis-inducing protein, HAP, induces bacterial cell death."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Rep (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1023/b:mole.0000043551.84883.c8"}], "href": "https://doi.org/10.1023/b:mole.0000043551.84883.c8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15560370"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15560370"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Annika Kratzel, Volker Thiel "}, {"type": "b", "children": [{"type": "t", "text": "RTN3 and RTN4: Architects of SARS-CoV-2 replication organelles."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.202306020"}], "href": "https://doi.org/10.1083/jcb.202306020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37318453"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37318453"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Agnieszka Kulczyńska-Przybik, Piotr Mroczko, Maciej Dulewicz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Implication of Reticulons (RTNs) in Neurodegenerative Diseases: From Molecular Mechanisms to Potential Diagnostic and Therapeutic Approaches."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms22094630"}], "href": "https://doi.org/10.3390/ijms22094630"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33924890"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33924890"}]}]}]}