Glycan regulation of cell-cell junction dynamics and architecture

点击翻译按钮获取中文摘要

Glycosylation is a common posttranslational modification of glycoproteins, glycolipids and proteoglycans that generates extracellular binding sites for galactose-specific lectins or galectins. Cadherins are glycoproteins involved in cell-cell contacts whose extracellular domain mediates homotypic interactions with adjacent cells and cytoplasmic domain interacts through catenins with the underlying actin cytoskeleton. We have shown that galectin-3 destabilizes cell-cell junctions and increases mobility of N-cadherin and the lipid raft-associated glycosphingolipid GM1 ganglioside within cell-cell junctions. We hypothesize that galectin-3 regulation of glycoprotein and glycolipid residency and dynamics in cell-cell junctions drives local endocytosis impacting the underlying actin cytoskeleton and junctional stability. In this proposal, we will study the role of galectin-3 and lipid rafts in the regulation of N-cadherin dynamics and cell-cell junction architecture.****Aim 1: Galectin lattice and cell-cell junction dynamics **We will characterize study the impact of galectin-3 and raft domains on N-cadherin, GM1 and galectin-3 endocytosis and F-actin dynamics at cell-cell junctions.****Aim 2: Mediators of galectin lattice regulation of junctional stability **We will test the role of glycosphingolipids and candidate signaling and actin-regulatory proteins on galectin-3 stabilization of cell-cell junctions and on the dynamics of junction-associated molecules.****Aim 3: The architecture of the cell-cell junction by super-resolution microscopy**We will use super resolution microscopy to study the organization of galectin-3, raft markers, N-cadherin, catenins and the underlying actin cytoskeleton in the cell-cell junction.**