{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ARHGAP45, also known as HMHA1, is a multifunctional Rho GTPase–activating protein that plays key roles in cytoskeletal regulation in both vascular and hematopoietic cells. In endothelial cells, ARHGAP45 acts as a Rac‐GAP to negatively regulate barrier function. Its activity limits basal endothelial integrity, as silencing ARHGAP45 enhances cell spreading, increases cellular surface area, promotes sprout formation, and improves migration and adaptation to shear stress—findings that underscore its role in modulating vascular permeability and remodeling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the hematopoietic compartment, ARHGAP45 is predominantly expressed and is critical for immune cell dynamics. It regulates naïve T‐cell deformability and motility, thereby controlling the entry of naïve T and B cells into lymph nodes, as well as influencing hematopoietic progenitor cell engraftment and thymus seeding. These functions illustrate how ARHGAP45 helps orchestrate lymphocyte trafficking and immune surveillance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in the regulation of actin dynamics, ARHGAP45 is the source of the minor histocompatibility antigen HA‐1. This antigen is recognized by donor T cells after allogeneic stem cell transplantation and is implicated in graft‐versus‐host as well as graft‐versus‐leukemia responses. In addition, aberrant expression of HMHA1/ARHGAP45 has been associated with enhanced proliferation, migration, invasion, and survival in melanoma cells, highlighting its potential contribution to tumor progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, ARHGAP45/HMHA1 emerges as a versatile regulator that, through its Rac-GAP–mediated modulation of the actin cytoskeleton, fine-tunes endothelial barrier properties and immune cell trafficking, while also participating in antigen presentation mechanisms that influence transplant outcomes and potentially tumor behavior.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "J Amado-Azevedo, N R Reinhard, J van Bezu, et al. 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