Kazrin C regulates endocytic recycling pathways and controls cell migration

Abstract

Kazrin C was identified in a screening for human proteins that affect endocytic traffic when overexpressed. Indeed, its depletion delays the transfer of Transferrin from sorting to the Rab11 containing endosomes, whereas it accelerates a short loop recycling pathway. Kazrin C is localized at endosomes containing Transferrin and Rab4 and it directly interacts with components of the clathrin coat, such as clathrin and ¿-adaptin, and with components of the actin cytoskeleton, such as the ARP2/3 complex and WASH. In addition, it interacts with several phosphoinositides, which have a role in the regulation of endocytic trafficking. Our hypothesis is that Kazrin C favours the long recycling route in opposition to the short recycling route, either by controlling actin polymerization, by influencing the endosomal phosphoinositide content and/or by promoting loading of cargo into AP-1 and clathrin transport intermediates. The balance between these two routes is known to be important in the control of cell migration: ¿5ß1 integrin is recycled through the long route and its presence at the plasma membrane promotes random migration, while ¿vß3 follows the short route and promotes directionally persistent migration. In agreement with this and our hypothesis, we have observed an increased persistance in the migration of Kazrin C depleted cells when compared to control cells.