Role of JAM-A in leukocyte transendothelial migration

Brigham And Women'S Hospital, Boston MA

Investigators

Abstract

[unreadable] DESCRIPTION (provided by applicant): Leukocyte transendothelial migration (TEM) is a critical component of the inflammatory response involving a sequence of events that work in concert to permit the extravasation of an adherent leukocyte. During this event, redistribution of the surface adhesion molecule, Junctional Adhesion Molecule-A (JAM-A) can be observed on both endothelial cells and polarized leukocytes. However, the role of JAM-A redistribution in TEM is not clear. [unreadable] [unreadable] The redistribution of JAM-A is likely mediated by cytoskeletal rearrangements coupled through binding to cytoskeletal linker proteins. Therefore, we propose to identify the cytoskeletal binding partners and binding sites and uncouple these linkages to determine the role of JAM-A redistribution in TEM. Specifically we propose to: 1) Identify cytoskeletal biding partners of JAM-A 2) Identify binding sites on the cytoplasmic tail of JAM-A 3) Determine the role of leukocyte JAM-A redistribution on TEM 4) Determine the role of endothelial JAM-A redistribution on TEM. [unreadable] [unreadable]