{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNorbin (also known as neurochondrin) is a multifunctional adaptor protein critically involved in neuronal development and synaptic function. It is widely expressed in the developing and adult central nervous system, where it modulates glutamatergic signaling by physically interacting with group I metabotropic glutamate receptors (mGluRs), particularly mGluR5. Through these interactions, Norbin promotes receptor cell surface localization, facilitates ligand‐induced receptor internalization, and thereby regulates synaptic plasticity, including long‐term potentiation and depression. In addition, Norbin influences adult hippocampal neurogenesis and has been linked to alterations in behavior such as depressive-like and schizophrenia-related phenotypes. Its subcellular targeting is further fine-tuned by post-translational modifications such as palmitoylation, ensuring proper endosomal localization and efficient signal transduction."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in receptor trafficking, Norbin directly interacts with key regulators of the actin cytoskeleton. It binds to the pleckstrin homology domain of the guanine-nucleotide exchange factor P-Rex1, thereby enhancing Rac1 activation. This interaction promotes membrane recruitment of both proteins, leading to changes in cell morphology such as cell spreading, lamellipodia formation, and membrane ruffling—cellular events that are essential for neurite outgrowth and proper neuronal wiring."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond the nervous system, Norbin functions as an adaptor in immune cells, where it acts as a suppressor of neutrophil-mediated innate immunity. In myeloid cells, Norbin limits GPCR-dependent signaling and thereby restrains neutrophil responsiveness, including degranulation, phagocytosis, reactive oxygen species production, and extracellular trap formation. The loss of Norbin in these cells results in enhanced bacterial clearance during infections, underscoring its critical role in maintaining immune homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Reiko Mochizuki, Minori Dateki, Kazuyuki Yanai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeted disruption of the neurochondrin/norbin gene results in embryonic lethality."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2003.09.153"}], "href": "https://doi.org/10.1016/j.bbrc.2003.09.153"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14559245"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14559245"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "R Istvánffy, D M Vogt Weisenhorn, T Floss, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of neurochondrin in the developing and adult mouse brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Genes Evol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00427-004-0396-2"}], "href": "https://doi.org/10.1007/s00427-004-0396-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15007648"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15007648"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Minori Dateki, Takuro Horii, Yoshitoshi Kasuya, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neurochondrin negatively regulates CaMKII phosphorylation, and nervous system-specific gene disruption results in epileptic seizure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M414033200"}], "href": "https://doi.org/10.1074/jbc.M414033200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15790563"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15790563"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hong Wang, Linda Westin, Yi Nong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Norbin is an endogenous regulator of metabotropic glutamate receptor 5 signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1178496"}], "href": "https://doi.org/10.1126/science.1178496"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20007903"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20007903"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Shinichiro Oku, Naoki Takahashi, Yuko Fukata, et al. "}, {"type": "b", "children": [{"type": "t", "text": "In silico screening for palmitoyl substrates reveals a role for DHHC1/3/10 (zDHHC1/3/11)-mediated neurochondrin palmitoylation in its targeting to Rab5-positive endosomes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.431676"}], "href": "https://doi.org/10.1074/jbc.M112.431676"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23687301"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23687301"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Hong Wang, Jennifer Warner-Schmidt, Santiago Varela, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Norbin ablation results in defective adult hippocampal neurogenesis and depressive-like behavior in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1510291112"}], "href": "https://doi.org/10.1073/pnas.1510291112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26195764"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26195764"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Prachi Ojha, Subhajit Pal, Samarjit Bhattacharyya "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of Metabotropic Glutamate Receptor Internalization and Synaptic AMPA Receptor Endocytosis by the Postsynaptic Protein Norbin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.1037-21.2021"}], "href": "https://doi.org/10.1523/JNEUROSCI.1037-21.2021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34907024"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34907024"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Dingxin Pan, Mark A Barber, Kirsti Hornigold, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Norbin Stimulates the Catalytic Activity and Plasma Membrane Localization of the Guanine-Nucleotide Exchange Factor P-Rex1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M115.686592"}], "href": "https://doi.org/10.1074/jbc.M115.686592"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26792863"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26792863"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Chiara Pantarelli, Dingxin Pan, Stephen Chetwynd, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The GPCR adaptor protein norbin suppresses the neutrophil-mediated immunity of mice to pneumococcal infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood Adv (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/bloodadvances.2020002782"}], "href": "https://doi.org/10.1182/bloodadvances.2020002782"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34402884"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34402884"}]}]}]}