PLXND1 is a type I transmembrane receptor for semaphorin family signaling molecules. PLXND1 has an extracellular SEMA binding domain, and a cytoplasmic tail containing RasGAP motifs and a RhoGTPase-binding domain. Upon ligand binding, PLXND1 undergoes conformational change and acquires GAP activity that inactivates downstream Rac/Ras signaling, leading to focal adhesion destabilization. The PLXND1 signaling pathway plays important roles in neuronal synapse formation, vascular branching, and thymocyte migration. Increased expression of PLXND1 is positively correlated with tumor stages in multiple cancer types. This is supported by gene knockdown experiments that suggest that SEMA/PLXND1 signaling may contribute metastatic progression.
[1] Gu, C. and Giraudo, E. (2013) Exp Cell Res 319, 1306-16.
[2] Gay, C.M. et al. (2011) Dev Biol 349, 1-19.
[3] Pecho-Vrieseling, E. et al. (2009) Nature 459, 842-6.
[4] Zygmunt, T. et al. (2011) Dev Cell 21, 301-14.
[5] Choi, Y.I. et al. (2008) Immunity 29, 888-98.
[6] Rehman, M. et al. (2016) PLoS One 11, e0164660.
[7] Tseng, C.H. et al. (2011) PLoS One 6, e19396.
[8] Casazza, A. et al. (2010) J Clin Invest 120, 2684-98.
