{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMYRIP (myosin‐VIIa‐ and Rab27a‐interacting protein), also known as Slac2c, acts as a crucial effector linking Rab27a‐associated organelles to components of the actin cytoskeleton. In retinal pigment epithelium cells, MYRIP interacts with myosin VIIa and Rab27a to tether melanosomes to the cortical actin network, ensuring their correct subcellular localization and proper local trafficking. Similar molecular interactions are observed in melanocytes, where MYRIP, through its conserved domains, couples Rab27a to the actin cytoskeleton and potentially to myosins, thereby capturing pigment‐containing organelles at the cell periphery."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn secretory cell systems, MYRIP plays multiple roles in regulating exocytosis. In pancreatic beta-cells, it associates with insulin granules via Rab27a where its actin-binding domain is essential for the final steps of hormone release, even in the absence of detectable myosin Va involvement. In endothelial cells, MYRIP forms part of a tripartite complex with Rab27a and myosin Va on mature Weibel-Palade bodies, anchoring these secretory granules to the peripheral actin network; this mechanism not only restricts premature secretion but is also critical for the full multimerization of von Willebrand factor. Live-cell imaging studies in other secretory systems have further revealed that by recruiting myosin Va and directly binding to actin, MYRIP limits fast, microtubule-dependent granule movements while promoting granule tethering at the plasma membrane, thereby coordinating granule transport and retention prior to release."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional functions for MYRIP include roles in other actin-based transport processes. During spermiogenesis, MYRIP is associated with intramanchette transport by partnering with myosin Va and Rab27 isoforms on F-actin tracks, suggesting a broader involvement in cell polarization and organelle redistribution. Moreover, genetic association studies have identified intronic variants in MYRIP as protective against age-related macular degeneration, supporting its significance in retinal pigment epithelium cell function and melanosome dynamics."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Aziz El-Amraoui, Jéan-Sebastien Schonn, Polonca Küssel-Andermann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MyRIP, a novel Rab effector, enables myosin VIIa recruitment to retinal melanosomes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Rep (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/embo-reports/kvf090"}], "href": "https://doi.org/10.1093/embo-reports/kvf090"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11964381"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11964381"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Mitsunori Fukuda, Taruho S Kuroda "}, {"type": "b", "children": [{"type": "t", "text": "Slac2-c (synaptotagmin-like protein homologue lacking C2 domains-c), a novel linker protein that interacts with Rab27, myosin Va/VIIa, and actin."}]}, {"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.M203862200"}], "href": "https://doi.org/10.1074/jbc.M203862200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12221080"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12221080"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Laurent Waselle, Thierry Coppola, Mitsunori Fukuda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of the Rab27 binding protein Slac2c/MyRIP in insulin exocytosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e03-01-0022"}], "href": "https://doi.org/10.1091/mbc.e03-01-0022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14517322"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14517322"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Thomas D Nightingale, Krupa Pattni, Alistair N Hume, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rab27a and MyRIP regulate the amount and multimeric state of VWF released from endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2008-09-181206"}], "href": "https://doi.org/10.1182/blood-2008-09-181206"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19270261"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19270261"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Inés Rojo Pulido, Thomas D Nightingale, François Darchen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Myosin Va acts in concert with Rab27a and MyRIP to regulate acute von-Willebrand factor release from endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Traffic (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1600-0854.2011.01248.x"}], "href": "https://doi.org/10.1111/j.1600-0854.2011.01248.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21740491"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21740491"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ianina L Conte, Nicola Hellen, Ruben Bierings, et al. 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