{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSynaptotagmin‐like protein 1 (SYTL1), also known as Slp1 or JFC1, functions as a Rab27 effector that orchestrates several aspects of vesicular trafficking and membrane docking. In melanocytes, SYTL1 binds the active, GTP‐loaded Rab27A via its synaptotagmin‐like homology domain, thereby directing the transport of melanosomes to peripheral dendritic tips."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In cytotoxic T lymphocytes, SYTL1, together with related family members, localizes predominantly to the plasma membrane and accumulates at the immunological synapse to facilitate the polarized exocytosis of secretory lysosomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In neutrophils, SYTL1 (termed JFC1 in this context) is implicated in modulating actin remodeling around secretory granules, enabling these organelles to traverse cortical actin barriers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn secretory cells of the prostate and platelets, SYTL1 plays a critical role in controlling the release of specific cargo. In prostate carcinoma cells, SYTL1 is an integral component of the exocytic machinery that differentially regulates the secretion of prostatic markers, including PSAP and PSA, with its expression being modulated by TNFα/NF‐κB signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In platelets, SYTL1 forms a trimeric complex together with Rab27 and Rap1GAP2; this complex functions to negatively regulate dense granule secretion, a process finely tuned through its C2A domain."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, SYTL1 interacts with the Fbw7‐γ isoform, whereby its binding stabilizes Fbw7‐γ and consequently promotes c‐Myc degradation, with cell cycle kinases such as Cdk2 modulating this interaction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in vesicular transport and secretion, SYTL1 contributes to oncogenic processes. In models of leukemogenesis, the homeoprotein MEIS1 directly induces SYTL1 expression, which in turn enhances leukemic cell migration and bone marrow engraftment by facilitating the intracellular trafficking of CXCR4."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In bladder cancer, transcription factor ELK1, in concert with HDAC2, represses SYTL1, a suppression that is associated with enhanced malignancy; intriguingly, m6A regulatory mechanisms have also been implicated in modulating SYTL1 expression and mediating natural killer cell anti‐tumor responses in this context."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Taruho S Kuroda, Mitsunori Fukuda, Hiroyoshi Ariga, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Slp homology domain of synaptotagmin-like proteins 1-4 and Slac2 functions as a novel Rab27A binding domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112414200"}], "href": "https://doi.org/10.1074/jbc.M112414200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11773082"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11773082"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Oliver Holt, Eiko Kanno, Giovanna Bossi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Slp1 and Slp2-a localize to the plasma membrane of CTL and contribute to secretion from the immunological synapse."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Traffic (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1600-0854.2008.00714.x"}], "href": "https://doi.org/10.1111/j.1600-0854.2008.00714.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18266782"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18266782"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jennifer L Johnson, Jlenia Monfregola, Gennaro Napolitano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Vesicular trafficking through cortical actin during exocytosis is regulated by the Rab27a effector JFC1/Slp1 and the RhoA-GTPase-activating protein Gem-interacting protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E11-12-1001"}], "href": "https://doi.org/10.1091/mbc.E11-12-1001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22438581"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22438581"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sergio D Catz, Bernard M Babior, Jennifer L Johnson "}, {"type": "b", "children": [{"type": "t", "text": "JFC1 is transcriptionally activated by nuclear factor-kappaB and up-regulated by tumour necrosis factor alpha in prostate carcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20020345"}], "href": "https://doi.org/10.1042/BJ20020345"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12137562"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12137562"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jennifer L Johnson, Beverly A Ellis, Deborah Noack, et al. 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