Kinesin‐1 mediates targeted recycling of the lateral border recycling compartment

Abstract

A critical step in the inflammatory response is transendothelial migration (TEM). Our lab has recently discovered a membrane compartment in endothelial cells (EC) that regulates TEM: The lateral border recycling compartment (LBRC). The LBRC contains a subset of membrane proteins, such as PECAM, CD99, and JAMA, which are required for TEM. During TEM, membrane from the LBRC is directed to the region of the EC where the leukocyte is transmigrating. This “targeted recycling” (TR) facilitates TEM by delivering LBRC membrane and proteins to the migrating leukocyte. Inhibiting targeted recycling of the LBRC blocks leukocyte TEM. Targeted recycling of the LBRC requires functional microtubules and kinesin motors. Microinjection of EC with an antibody against the conserved motor domain of kinesin inhibited TR and TEM to a similar magnitude as blocking PECAM or depolymerizing microtubules. We sought to identify the specific kinesin(s) that mediate targeted recycling. Preliminary experiments suggested the KIF5b gene product, kinesin‐1 as a likely candidate. Microinjection of EC with a kinesin‐1 mAb blocked TEM. Knocking down kinesin‐1 in EC decreased targeted recycling of LBRC and leukocyte TEM in preliminary experiments. This suggests that kinesin‐1 is a major molecular motor necessary for LBRC transport along microtubules during TR. Supported by an AHA Midwest Affiliate Predoctoral Fellowship and NIH R01 HL046849.