{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ELMO1 is a versatile intracellular adaptor protein that, by forming complexes with DOCK family members, orchestrates Rac GTPase activation to couple extracellular signals to cytoskeletal reorganization. In multiple systems, the DOCK–ELMO1 module is essential for directional cell migration and invasion, as demonstrated by studies showing that alterations in ELMO1 promote invasive phenotypes in esophageal adenocarcinoma, gliomas, and breast cancer cells through Rac1‐dependent mechanisms."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " Structural and functional analyses further reveal that ELMO1, working together with DOCK180 or DOCK2, serves as a critical component of a bipartite guanine nucleotide exchange factor complex required for efficient Rac activation and subsequent cell migration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "8"}]}, {"type": "t", "text": " Beyond its role in cell motility, ELMO1 is pivotal for phagocytic clearance; it relays signals from receptors such as BAI1 to trigger Rac-mediated engulfment of apoptotic cells by neural progenitors and professional phagocytes, a function critical for tissue homeostasis and neurogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "13"}]}, {"type": "t", "text": " In addition, genetic studies have linked variants and elevated expression of ELMO1 to the pathogenesis of diabetic nephropathy"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "16"}]}, {"type": "t", "text": ", while upregulation of ELMO1 also appears to enhance the directional migration of mesenchymal stem cells in ankylosing spondylitis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": " Finally, studies in myoblasts further underscore the importance of ELMO1 in mediating cell–cell fusion during muscle development, as loss of ELMO1 or disruption of its binding to receptors such as BAI3 severely compromises myoblast fusion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": " Collectively, these findings position ELMO1 as a central integrator of signaling pathways that regulate cell migration, phagocytosis, and tissue remodeling in both physiological and pathological contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}, {"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Austin M Dulak, Petar Stojanov, Shouyong Peng, et al. 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