PLXNA1

PLXNA1 refers to the human gene encoding Plexin-A1, a single-pass transmembrane receptor in the plexin family. It binds class 3 semaphorins and mediates signaling that guides axons and regulates neuronal development, with roles in immune responses and angiogenesis. It often requires co-receptors such as neuropilins for semaphorin binding.

Structure and signaling: Plexin-A1 has an extracellular sema domain, multiple PSI and IPT-like domains, a single transmembrane helix, and a cytoplasmic region containing a GAP-like domain that modulates small GTPases to control cytoskeletal dynamics. Ligand binding induces receptor conformational changes and engages downstream effectors like CRMPs, Rac, Rho, and Cdc42 pathways.

Ligands and interactions: Primary ligands are class 3 semaphorins, especially Sema3A, often in complex with neuropilin-1 (NRP1). Plexin-A1 also participates in signaling with other semaphorins and may mediate diverse cellular responses, including repulsion or attraction depending on context.

Expression and function: PLXNA1 is broadly expressed in the nervous system and various tissues; it guides developing axons, neuronal migration, dendritic patterning, and synapse formation. In adulthood, it contributes to neuronal plasticity and may influence immune cell migration and vascular remodeling.

Clinical relevance: Altered PLXNA1 signaling has been linked to cancers, where it may affect tumor cell migration and invasion, and to neurodevelopmental disorders and injury responses. Research continues to define its precise roles and therapeutic potential.