Plexin-A receptor (Plexin-A)

Plexin-A receptors are a family of large transmembrane cell surface receptors that serve as the main signaling receptors for the semaphorin family of proteins. The family consists of four members in humans: Plexin-A1, Plexin-A2, Plexin-A3, and Plexin-A4. These receptors possess an extracellular Sema domain (for ligand binding) followed by alternating PSI and IPT domains, and a highly conserved intracellular region with a split GTPase-activating protein (GAP) domain separated by a Rho-GTPase binding domain (RBD). Upon binding semaphorin ligands, often with the involvement of neuropilin co-receptors, they transduce signals critical for neuronal axon guidance, immune cell regulation, angiogenesis, and cell migration. Their signaling involves changes in small GTPase activity and is tightly controlled through autoinhibition and activation mechanisms. Plexin-A signaling is implicated in cancer progression, nervous system development, inflammation, and vascular biology. No approved clinical drugs directly target Plexin-A receptors, and therapeutic modulation poses risks due to their broad roles in development and tissue homeostasis.

Other names

Plexin Class APlexin-A1Plexin-A2Plexin-A3Plexin-A4semaphorin receptor

Modulation of semaphorin-plexin signaling (ligand binding triggers conformational changes and signal transduction). Regulation of intracellular GTPase signaling via GAP domain, affecting small GTPases (e.g., Ras, Rho, Rap). Downstream modulation of cytoskeletal and adhesive machinery, impacting cell migration, axon guidance, and immune response.