{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The calcium‐dependent activator protein for secretion (CADPS), also known as CAPS, comprises two major isoforms (CAPS1/CADPS1 and CAPS2/CADPS2) that play central roles in regulated vesicular exocytosis in both neurons and neuroendocrine cells. These proteins are essential for priming secretory vesicles and enabling the release of a wide variety of cargoes, including classical neurotransmitters and neuropeptides such as brain‐derived neurotrophic factor (BDNF) and neurotrophin‐3 (NT‐3)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In neurons, CAPS1 interacts with SNARE proteins—most notably, it binds to an “open” conformation of syntaxin‐1 via its C‐terminal domain—to promote the fusion competence of docked vesicles at presynaptic terminals. This interaction is critical for its synaptic enrichment and is necessary for proper dense-core vesicle (DCV) exocytosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": " Furthermore, forebrain‐specific CAPS1 deletion reduces the fraction of docked vesicles at hippocampal synapses, impairs synaptic transmission and long‐term potentiation, and leads to deficits in hippocampus‐dependent learning, underscoring its indispensable role in synaptic plasticity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In parallel, CAPS2 is selectively involved in the release of neurotrophins. Its precise subcellular localization is crucial for axonal secretion of BDNF and NT‐3, and alterations in CAPS2 splicing—as evidenced by the identification of a rare splice variant overrepresented in autism spectrum disorders—disrupt proper neurotrophin distribution and impair cerebellar development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Notably, RNA editing of the CADPS transcript further modulates CAPS1 function by enhancing its synaptic localization and influencing short-term plasticity at inhibitory synapses (for instance, increased short-term depression), thereby fine-tuning neurotransmission."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, in vivo studies reveal that conditional depletion of CAPS1 in the forebrain leads to impaired vesicle docking and synaptic deficits that compromise hippocampal plasticity and learning processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Beyond neuronal functions, dysregulation of CADPS expression has been implicated in non-neuronal contexts. For example, overexpression of CAPS1 in colorectal cancer cells alters exosome content and promotes cell migration, while reduced expression levels of CADPS may contribute to neuroprotective pathways in dopamine neurons."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies underscore that CADPS proteins are pivotal modulators of secretion across diverse cellular contexts. By orchestrating the priming and fusion of secretory vesicles, they regulate synaptic transmission and plasticity, neurotrophin release, and even cellular communication in cancer. This multifaceted role in both the nervous system and peripheral tissues highlights their significance in maintaining physiological function and their potential contribution to disease states when dysregulated.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tetsushi Sadakata, Makoto Itakura, Shunji Kozaki, et al. 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