{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNAPA, the gene product encoding alpha‐soluble NSF attachment protein (alpha‐SNAP), is a critical mediator of membrane fusion events. In the context of exocytosis, NAPA is indispensable for facilitating the acrosome reaction in spermatozoa by acting in a pre‐fusion step, where it partners with NSF and SNARE proteins to enable membrane merging prior to Ca²⁺ release."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, it contributes to the functional assembly of store‐operated calcium entry complexes by binding high affinity regions on Stim1 and Orai1, which is crucial for determining Ca²⁺ selectivity and channel assembly."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in exocytosis, NAPA has emerged as a key regulator of intracellular trafficking pathways that impact cellular homeostasis. Its downregulation triggers autophagic flux via a non‐canonical pathway involving mTOR signaling attenuation and Golgi fragmentation, underscoring a negative regulatory role in autophagy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Concurrently, proper NAPA function promotes cell survival by maintaining Golgi to endoplasmic reticulum trafficking required for optimal Bcl-2 expression, thereby protecting epithelial cells from apoptosis under cytotoxic conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn epithelial and endothelial systems, NAPA is essential for establishing and maintaining intercellular adhesions and extracellular matrix (ECM) contacts. It facilitates the formation of adherens and tight junctions by regulating Golgi-dependent expression and trafficking of junctional proteins such as E-cadherin and p120-catenin."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Furthermore, through its selective interaction with Gα12, NAPA stabilizes VE-cadherin at the plasma membrane to preserve endothelial barrier function"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", and it reinforces integrin-based ECM adhesion by ensuring proper glycosylation and surface delivery of β1-integrin, which in turn sustains focal adhesion kinase and paxillin signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Notably, reductions in NAPA levels in neuronal tissues correlate with enhanced seizure susceptibility, suggesting its broader importance in maintaining cellular homeostasis in the brain."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "C N Tomes, G A De Blas, M A Michaut, et al. "}, {"type": "b", "children": [{"type": "t", "text": "alpha-SNAP and NSF are required in a priming step during the human sperm acrosome reaction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Hum Reprod (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/molehr/gah126"}], "href": "https://doi.org/10.1093/molehr/gah126"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15542541"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15542541"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ramanagouda Ramanagoudr-Bhojappa, Yong Miao, Monika Vig "}, {"type": "b", "children": [{"type": "t", "text": "High affinity associations with α-SNAP enable calcium entry via Orai1 channels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0258670"}], "href": "https://doi.org/10.1371/journal.pone.0258670"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34653219"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34653219"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Nayden G Naydenov, Gianni Harris, Victor Morales, et al. 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