PlexinD1

PlexinD1 is a transmembrane receptor in the plexin family that serves as a receptor for semaphorin guidance cues. In humans, the PLXND1 gene encodes PlexinD1, which is expressed in multiple tissues, including neural tissue and endothelial cells. The protein participates in signaling pathways that regulate cell movement, axon guidance, and vascular development.

The extracellular region of PlexinD1 contains a sema domain responsible for ligand binding, followed by PSI and other domains. The intracellular region features a RasGAP-like domain that transduces signals to small GTPases. PlexinD1 signaling can be triggered by semaphorins, particularly semaphorin 3E, and may influence cytoskeletal dynamics and cell adhesion to steer migration.

PlexinD1 primarily mediates responses to semaphorin 3E (Sema3E). In the Sema3E-PlexinD1 axis, binding by Sema3E can induce repulsion of migrating axons and constraining endothelial cell movement, thereby shaping neural circuits and vascular patterning. In some tissues, PlexinD1 can signal independently of neuropilins, while in other contexts co-receptors modulate signaling and responsiveness.

PlexinD1 has important roles in development, guiding neuronal connections and contributing to embryonic vascular organization, including arterial-venous differentiation and remodeling of endothelial networks. Loss or dysregulation of PlexinD1 in model organisms leads to defects in neural and vascular patterning, underscoring its role in coordinated tissue formation.

Dysregulation of PlexinD1 signaling has also been studied in cancer and angiogenesis. Altered PlexinD1 expression or Sema3E-PlexinD1 signaling can affect tumor vasculature and metastatic behavior in certain cancers, reflecting its broader influence on cell guidance and movement.