{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DOC2B is a multifunctional, double C2‐domain protein that plays a central role in regulated vesicle fusion in both neuronal and non‐neuronal cell types. In neurons, DOC2B acts as a high‐affinity calcium sensor that is recruited from the cytosol to the plasma membrane in response to modest elevations in intracellular Ca²⁺. This translocation facilitates its interaction with SNARE proteins—competing with canonical Ca²⁺ sensors like synaptotagmin‐1—to regulate spontaneous, synchronous, and asynchronous neurotransmitter release, and to modulate the pool of fusion‐competent vesicles (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " In neuroendocrine cells and chromaffin cells, DOC2B functions as a calcium‐dependent priming factor, enhancing both vesicle docking and fusion kinetics, thereby promoting efficient catecholamine secretion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, DOC2B is critical for the regulation of insulin secretion and insulin‐stimulated glucose uptake. In pancreatic β‐cells, DOC2B translocates to the plasma membrane upon glucose‐induced Ca²⁺ elevation and undergoes specific phosphorylation (on tyrosine 301 or serine 34) by kinases such as YES and atypical PKCι. These posttranslational modifications facilitate its interaction with SNARE components including syntaxin‐4 and VAMP2, as well as ERM proteins, thereby enhancing the docking and fusion of insulin granules and promoting the second phase of insulin release."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "9"}]}, {"type": "t", "text": " In addition, DOC2B is indispensable for the insulin‐stimulated translocation of GLUT4 vesicles in adipocytes and skeletal muscle, where its enrichment improves peripheral insulin sensitivity and overall glucose homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, DOC2B functions as a versatile regulator of exocytosis by coupling Ca²⁺ signals to the molecular machinery required for vesicle priming and fusion. Its finely tuned Ca²⁺ sensitivity and regulated interactions with SNARE components ensure precise timing of neurotransmitter release and insulin secretion. Consequently, DOC2B is emerging as a key effector in both neuronal communication and metabolic regulation.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alexander J Groffen, Sascha Martens, Rocío Díez Arazola, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Doc2b synchronizes secretion from chromaffin cells by stimulating fast and inhibiting sustained release."}]}, {"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.2656-13.2013"}], "href": "https://doi.org/10.1523/JNEUROSCI.2656-13.2013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24133251"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24133251"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Alexander J A Groffen, Reut Friedrich, Elisabeth C Brian, et al. 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