Dynamic trafficking and turnover of JAM-C is essential for endothelial cell migration

by Katja B. Kostelnik, Amy Barker, Christopher Schultz, Tom P. Mitchell, Vinothini Rajeeve, Ian J. White, Michel Aurrand-Lions, Sussan Nourshargh, Pedro Cutillas, Thomas D. Nightingale

Junctional complexes between endothelial cells form a dynamic barrier that hinders passive diffusion of blood constituents into interstitial tissues. Remodelling of junctions is an essential process during leukocyte trafficking, vascular permeability, and angiogenesis. However, for many junctional proteins, the mechanisms of junctional remodelling have yet to be determined. Here, we used receptor mutagenesis, horseradish peroxidase (HRP), and ascorbate peroxidase 2 (APEX-2) proximity labelling, alongside light and electron microscopy (EM), to map the intracellular trafficking routes of junctional adhesion molecule-C (JAM-C). We found that JAM-C cotraffics with receptors associated with changes in permeability such as vascular endothelial cadherin (VE-Cadherin) and neuropilin (NRP)-1 and 2, but not with junctional proteins associated with the transmigration of leukocytes. Dynamic JAM-C trafficking and degradation are necessary for junctional remodelling during cell migration and angiogenesis. By identifying new potential trafficking machinery, we show that a key point of regulation is the ubiquitylation of JAM-C by the E3 ligase Casitas B-lineage lymphoma (CBL), which controls the rate of trafficking versus lysosomal degradation.

Source link

Related posts

Upstream Open Reading Frame and Phosphate-Regulated Expression of Rice OsNLA1 Controls Phosphate Transport and Reproduction


More Urban Botanical Art


Faculty position in Evolutionary Developmental Biology at the University of Oklahoma


This website uses cookies to improve your experience. We'll assume you're ok with this, but you can opt-out if you wish. Accept Read More

Privacy & Cookies Policy