{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSortilin – the protein product of SORT1 – is emerging as a critical regulator of lipoprotein metabolism and cardiovascular risk. Genome‐wide association studies have repeatedly linked common variants near SORT1 with plasma levels of low‐density lipoprotein cholesterol, triglycerides and myocardial infarction risk. Functional investigations in human liver and animal models demonstrate that sortilin governs the intracellular sorting of apolipoprotein B100–containing lipoprotein particles, modulating very low–density lipoprotein secretion and promoting LDL catabolism. In addition, insulin‐dependent signaling and population–specific genetic variation influence hepatic sortilin expression, contributing to vascular calcification, altered lipoprotein profiles, and overall cardiovascular risk."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its metabolic role, sortilin functions as a versatile intracellular sorting receptor that directs diverse cargoes toward lysosomal or recycling pathways. Experimental studies have shown that sortilin participates in the lysosomal targeting of sphingolipid activator proteins and binds ligands such as apolipoprotein A–V, thereby influencing lipid–associated as well as general protein trafficking. Moreover, sortilin has been implicated in the intracellular routing of enzymes and membrane proteins including BACE1 and the amyloid precursor protein, as well as in the biogenesis of insulin-responsive vesicles and in the degradation of the sodium–chloride cotransporter. These observations underscore a fundamental role for sortilin in controlling protein processing and cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "29"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSortilin also modulates neurotrophic and oncogenic signaling pathways that impact both neurodegenerative disorders and cancer. As a co–receptor with p75 neurotrophin receptor, sortilin mediates the binding and internalization of pro–neurotrophins—a process linked to neuronal apoptosis and implicated in frontotemporal lobar degeneration. Additionally, sortilin regulates the secretion and cellular uptake of growth factors such as progranulin and brain–derived neurotrophic factor, influences exosome assembly, and modulates receptor internalization events including those involving EGFR and neurotensin receptors. Altered sortilin expression and splicing, as observed in depression, certain cancers and Alzheimer’s disease, suggest that dysregulation of sortilin-dependent trafficking contributes to disease pathogenesis and may offer novel therapeutic targets."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "30", "end_ref": "40"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sekar Kathiresan, Olle Melander, Candace Guiducci, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.75"}], "href": "https://doi.org/10.1038/ng.75"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18193044"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18193044"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Rahul C Deo, David Reich, Arti Tandon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic differences between the determinants of lipid profile phenotypes in African and European Americans: the Jackson Heart Study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1000342"}], "href": "https://doi.org/10.1371/journal.pgen.1000342"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19148283"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19148283"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sekar Kathiresan, Benjamin F Voight, Shaun Purcell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.327"}], "href": "https://doi.org/10.1038/ng.327"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19198609"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19198609"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Marcus E Kleber, Wilfried Renner, Tanja B Grammer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of the single nucleotide polymorphism rs599839 in the vicinity of the sortilin 1 gene with LDL and triglyceride metabolism, coronary heart disease and myocardial infarction. The Ludwigshafen Risk and Cardiovascular Health Study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Atherosclerosis (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.atherosclerosis.2009.09.068"}], "href": "https://doi.org/10.1016/j.atherosclerosis.2009.09.068"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19837406"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19837406"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Stephanie L Swift, Julie E Burns, Norman J Maitland "}, {"type": "b", "children": [{"type": "t", "text": "Altered expression of neurotensin receptors is associated with the differentiation state of prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-09-1252"}], "href": "https://doi.org/10.1158/0008-5472.CAN-09-1252"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20048080"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20048080"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Kiran Musunuru, Alanna Strong, Maria Frank-Kamenetsky, et al. "}, {"type": "b", "children": [{"type": "t", "text": "From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature09266"}], "href": "https://doi.org/10.1038/nature09266"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20686566"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20686566"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Mads Kjolby, Olav M Andersen, Tilman Breiderhoff, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sort1, encoded by the cardiovascular risk locus 1p13.3, is a regulator of hepatic lipoprotein export."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Metab (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cmet.2010.08.006"}], "href": "https://doi.org/10.1016/j.cmet.2010.08.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20816088"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20816088"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Samuli Ripatti, Emmi Tikkanen, Marju Orho-Melander, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A multilocus genetic risk score for coronary heart disease: case-control and prospective cohort analyses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lancet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/S0140-6736(10)61267-6"}], "href": "https://doi.org/10.1016/S0140-6736(10"}, {"type": "t", "text": "61267-6) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20971364"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20971364"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yohann Demont, Cyril Corbet, Adeline Page, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pro-nerve growth factor induces autocrine stimulation of breast cancer cell invasion through tropomyosin-related kinase A (TrkA) and sortilin protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.211714"}], "href": "https://doi.org/10.1074/jbc.M110.211714"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22128158"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22128158"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Alanna Strong, Qiurong Ding, Andrew C Edmondson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hepatic sortilin regulates both apolipoprotein B secretion and LDL catabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI63563"}], "href": "https://doi.org/10.1172/JCI63563"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22751103"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22751103"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Alanna Strong, Kevin Patel, Daniel J Rader "}, {"type": "b", "children": [{"type": "t", "text": "Sortilin and lipoprotein metabolism: making sense out of complexity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Opin Lipidol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/MOL.0000000000000110"}], "href": "https://doi.org/10.1097/MOL.0000000000000110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25101658"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25101658"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Jibiao Li, David J Matye, Tiangang Li "}, {"type": "b", "children": [{"type": "t", "text": "Insulin resistance induces posttranslational hepatic sortilin 1 degradation in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M115.641225"}], "href": "https://doi.org/10.1074/jbc.M115.641225"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25805502"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25805502"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Claudia Goettsch, Joshua D Hutcheson, Masanori Aikawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sortilin mediates vascular calcification via its recruitment into extracellular vesicles."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI80851"}], "href": "https://doi.org/10.1172/JCI80851"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26950419"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26950419"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Claudia Goettsch, Hiroshi Iwata, Joshua D Hutcheson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serum Sortilin Associates With Aortic Calcification and Cardiovascular Risk in Men."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/ATVBAHA.116.308932"}], "href": "https://doi.org/10.1161/ATVBAHA.116.308932"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28279970"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28279970"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Seyedeh M Zekavat, Sanni Ruotsalainen, Robert E Handsaker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-04668-w"}], "href": "https://doi.org/10.1038/s41467-018-04668-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29973585"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29973585"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Stephane Lefrancois, Jibin Zeng, A Jacob Hassan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The lysosomal trafficking of sphingolipid activator proteins (SAPs) is mediated by sortilin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/emboj/cdg629"}], "href": "https://doi.org/10.1093/emboj/cdg629"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14657016"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14657016"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Jun Shi, Konstantin V Kandror "}, {"type": "b", "children": [{"type": "t", "text": "The luminal Vps10p domain of sortilin plays the predominant role in targeting to insulin-responsive Glut4-containing vesicles."}]}, {"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.M608971200"}], "href": "https://doi.org/10.1074/jbc.M608971200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17220298"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17220298"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Stefan K Nilsson, Stine Christensen, Merete K Raarup, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endocytosis of apolipoprotein A-V by members of the low density lipoprotein receptor and the VPS10p domain receptor families."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M802721200"}], "href": "https://doi.org/10.1074/jbc.M802721200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18603531"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18603531"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "V Kaddai, J Jager, T Gonzalez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of TNF-alpha in abnormal adipocyte and muscle sortilin expression in obese mice and humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetologia (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00125-009-1273-3"}], "href": "https://doi.org/10.1007/s00125-009-1273-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19219422"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19219422"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "K Nakayama, T Bayasgalan, K Yamanaka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Large scale replication analysis of loci associated with lipid concentrations in a Japanese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.2008.064063"}], "href": "https://doi.org/10.1136/jmg.2008.064063"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19487539"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19487539"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Bo Zhou, Jieqiu Zhuang, Dingying Gu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "WNK4 enhances the degradation of NCC through a sortilin-mediated lysosomal pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Soc Nephrol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1681/ASN.2008121275"}], "href": "https://doi.org/10.1681/ASN.2008121275"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19875813"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19875813"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Dan Feng, Taeho Kim, Engin Ozkan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular and structural insight into proNGF engagement of p75NTR and sortilin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2009.12.030"}], "href": "https://doi.org/10.1016/j.jmb.2009.12.030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20036257"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20036257"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Gina M Finan, Hirokazu Okada, Tae-Wan Kim "}, {"type": "b", "children": [{"type": "t", "text": "BACE1 retrograde trafficking is uniquely regulated by the cytoplasmic domain of sortilin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.170217"}], "href": "https://doi.org/10.1074/jbc.M110.170217"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21245145"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21245145"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Jacob Tauris, Camilla Gustafsen, Erik Ilsø Christensen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proneurotrophin-3 may induce Sortilin-dependent death in inner ear neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Neurosci (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1460-9568.2010.07556.x"}], "href": "https://doi.org/10.1111/j.1460-9568.2010.07556.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21261755"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21261755"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Sarah Felice Evans, Krithi Irmady, Katya Ostrow, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neuronal brain-derived neurotrophic factor is synthesized in excess, with levels regulated by sortilin-mediated trafficking and lysosomal degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.219675"}], "href": "https://doi.org/10.1074/jbc.M111.219675"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21730062"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21730062"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Maria Francisca Coutinho, Maria João Prata, Sandra Alves "}, {"type": "b", "children": [{"type": "t", "text": "A shortcut to the lysosome: the mannose-6-phosphate-independent pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Metab (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymgme.2012.07.012"}], "href": "https://doi.org/10.1016/j.ymgme.2012.07.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22884962"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22884962"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Mercedes Prudencio, Karen R Jansen-West, Wing C Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Misregulation of human sortilin splicing leads to the generation of a nonfunctional progranulin receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1211577110"}], "href": "https://doi.org/10.1073/pnas.1211577110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23236149"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23236149"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Camilla Gustafsen, Simon Glerup, Lone Tjener Pallesen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sortilin and SorLA display distinct roles in processing and trafficking of amyloid precursor protein."}]}, {"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.2371-12.2013"}], "href": "https://doi.org/10.1523/JNEUROSCI.2371-12.2013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23283322"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23283322"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Chutikarn Butkinaree, Maryssa Canuel, Rachid Essalmani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Amyloid Precursor-like Protein 2 and Sortilin Do Not Regulate the PCSK9 Convertase-mediated Low Density Lipoprotein Receptor Degradation but Interact with Each Other."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M115.647180"}], "href": "https://doi.org/10.1074/jbc.M115.647180"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26085104"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26085104"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Valérie Navarro, Jean-Pierre Vincent, Jean Mazella "}, {"type": "b", "children": [{"type": "t", "text": "Shedding of the luminal domain of the neurotensin receptor-3/sortilin in the HT29 cell line."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0006-291x(02)02564-0"}], "href": "https://doi.org/10.1016/s0006-291x(02"}, {"type": "t", "text": "02564-0) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12419319"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12419319"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Anne Morinville, Stéphane Martin, Mariette Lavallée, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Internalization and trafficking of neurotensin via NTS3 receptors in HT29 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biochem Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biocel.2004.04.013"}], "href": "https://doi.org/10.1016/j.biocel.2004.04.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15313463"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15313463"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Anne-Laure Fauchais, Fabrice Lalloué, Marie-Claude Lise, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of endogenous brain-derived neurotrophic factor and sortilin in B cell survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.181.5.3027"}], "href": "https://doi.org/10.4049/jimmunol.181.5.3027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18713973"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18713973"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Minerva M Carrasquillo, Alexandra M Nicholson, NiCole Finch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide screen identifies rs646776 near sortilin as a regulator of progranulin levels in human plasma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2010.11.002"}], "href": "https://doi.org/10.1016/j.ajhg.2010.11.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21087763"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21087763"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Hussein Akil, Aurélie Perraud, Carole Mélin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fine-tuning roles of endogenous brain-derived neurotrophic factor, TrkB and sortilin in colorectal cancer cell survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0025097"}], "href": "https://doi.org/10.1371/journal.pone.0025097"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21966426"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21966426"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Wing C Lee, Sandra Almeida, Mercedes Prudencio, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeted manipulation of the sortilin-progranulin axis rescues progranulin haploinsufficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddt534"}], "href": "https://doi.org/10.1093/hmg/ddt534"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24163244"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24163244"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Cornelia M Wilson, Thomas Naves, François Vincent, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sortilin mediates the release and transfer of exosomes in concert with two tyrosine kinase receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.149336"}], "href": "https://doi.org/10.1242/jcs.149336"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25037567"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25037567"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "H N Buttenschøn, D Demontis, M Kaas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased serum levels of sortilin are associated with depression and correlated with BDNF and VEGF."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Transl Psychiatry (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/tp.2015.167"}], "href": "https://doi.org/10.1038/tp.2015.167"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26556286"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26556286"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Fatemeh Mohagheghi, Mercedes Prudencio, Cristiana Stuani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TDP-43 functions within a network of hnRNP proteins to inhibit the production of a truncated human SORT1 receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddv491"}], "href": "https://doi.org/10.1093/hmg/ddv491"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26614389"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26614389"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Sam Faulkner, Philip Jobling, Christopher W Rowe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neurotrophin Receptors TrkA, p75"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "NTR"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": ", and Sortilin Are Increased and Targetable in Thyroid Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajpath.2017.09.008"}], "href": "https://doi.org/10.1016/j.ajpath.2017.09.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29037860"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29037860"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Hussein Al-Akhrass, Thomas Naves, François Vincent, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sortilin limits EGFR signaling by promoting its internalization in lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-017-01172-5"}], "href": "https://doi.org/10.1038/s41467-017-01172-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29084952"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29084952"}]}]}]}