Plexin A1 is found in both the nervous and immune systems. Its external Sema domain is also shared by semaphorin proteins. In the nervous system, Plexin A1 mediates Sema3A axon guidance function by interacting with the Sema3A coreceptor neuropilin, resulting in actin depolarization and cell repulsion [, ]. In the immune system, Plexin A1 mediates Sema6D signaling by binding to the Sema6D-Trem2-DAP12 complex on immune cells and osteoclasts to promote Rac activation and DAP12 phosphorylation []. In gene profiling experiments, Plexin A1 was identified as a CIITA (class II transactivator) regulated gene in primary dendritic cells (DCs) []. The Sema domain is located at the N terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as a ligand-recognition and -binding module.
