PlexinD

Plexin-D1, also known as Plexin-D1 receptor or PLXND1, is a member of the plexin family of transmembrane receptors for semaphorins. In humans it is encoded by the PLXND1 gene. Plexin-D1 functions as a signaling receptor that transduces guidance cues for neuronal axon navigation and vascular development, and it can influence cell migration and tissue morphogenesis in various contexts.

The receptor has a characteristic extracellular region that includes a sema domain and several PSI (plexin-semaphorin-integrin) domains, a single transmembrane segment, and a cytoplasmic region containing a Ras GTPase-activating protein (GAP)-like domain. The cytoplasmic region transduces signals to regulate small GTPases, leading to changes in the actin cytoskeleton and cell adhesion. Plexin-D1 often forms signaling complexes with neuropilins to mediate responses to class 3 semaphorins, though certain ligands, notably semaphorin 3E, can bind Plexin-D1 directly without neuropilins.

Biological roles of Plexin-D1 include guiding axons during neural development and shaping vascular patterning and endothelial behavior during angiogenesis. In development, Plexin-D1 signaling contributes to the proper organization of neural and vascular networks. In adults and in disease models, Plexin-D1 is studied for its involvement in immune cell motility, tumor vasculature, and cancer metastasis, with effects that appear to be context-dependent.

Genetic alterations or dysregulated Plexin-D1 signaling have been investigated in several diseases, and ongoing research aims to clarify its exact functions and therapeutic potential in neurodevelopmental, vascular, and oncologic contexts.