Plexin, small GTPases and their interactions with the calcium binding protein, Calmodulin: a possible mechanism for calcium to influence cell motility

Abstract

The plexin family is a group of transmembrane receptor proteins that are activated and function in cell motility by binding to small GTPases at their intracellular region. The interactions between plexin and the small GTPases such as Rac‐1 and Ras are well documented. The small GTPases regulate the activity of plexin by cooperating with extracellular semaphorin ligands to initiate a cellular response. However, there is evidence that the small GTPases are not the sole regulators of plexin. Plexin signaling is known to be sensitive to calcium and thus it is possible that a calcium binding protein, such as calmodulin, may have a role in regulating plexin's activity. We have found several putative calmodulin binding sites in plexins based on predictions from the calmodulin Target Database. Even if binding of calmodulin to plexin is not direct, but calmodulin is known to bind several of the plexin associated GTPases. Thus, it is possible that calmodulin regulates plexin by inhibiting the GTPases in their binding to plexin. In order to resolve the mode of calmodulin influence, we are currently studying the interaction of calmodulin with plexins and GTPases using isothermal titration calorimetry.