ARHGAPs

ARHGAPs, or Rho GTPase-activating proteins, are a diverse family of enzymes that regulate the activity of Rho family GTPases, a group of small signaling GTPases involved in many cellular processes including cytoskeletal organization, cell migration, proliferation, and survival. The primary function of ARHGAPs is to accelerate the intrinsic GTPase activity of Rho proteins, converting them from an active GTP-bound state to an inactive GDP-bound state. This inactivation is crucial for the spatiotemporal control of signaling pathways that govern cell behavior.

The ARHGAP family is subdivided into several classes based on domain architecture. Most members contain a conserved RhoGAP domain, while others are characterized by additional regulatory modules such as BAR domains, PH domains, or SH3 domains. Common examples include p190-RhoGAP, which has a dual RhoGAP domain and is involved in focal adhesion turnover; DLC1, containing a SAM and START domain, functions as a tumor suppressor; and ARHGAP11, which influences neuronal migration during cortical development.

Alterations in ARHGAP function have been linked to various diseases. Loss-of-function mutations in ARHGAP1 and ARHGAP22 have been implicated in certain cancers due to unchecked Rho signaling. Similarly, mutations in ARHGAP11A are associated with microcephaly, highlighting the importance of precise Rho regulation during neurodevelopment. Because of their regulatory role, ARHGAPs represent promising targets for therapeutic intervention in conditions ranging from metastatic cancer to neurodevelopmental disorders.

Overall, ARHGAPs serve as critical modulators that maintain cellular homeostasis by fine‑tuning the activity of Rho GTPases, thereby influencing a wide array of physiological and pathological processes.