Skip to Main content Skip to Navigation
Journal articles

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

Abstract : 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.
Complete list of metadata

Cited literature [70 references]  Display  Hide  Download
Contributor : Myriam Bodescot Connect in order to contact the contributor
Submitted on : Wednesday, January 8, 2020 - 4:20:32 PM
Last modification on : Wednesday, November 3, 2021 - 4:41:44 AM
Long-term archiving on: : Thursday, April 9, 2020 - 10:39:00 PM


Publication funded by an institution




Katja Kostelnik, Amy Barker, Christopher Schultz, Tom Mitchell, Vinothini Rajeeve, et al.. Dynamic trafficking and turnover of JAM-C is essential for endothelial cell migration. PLoS Biology, Public Library of Science, 2019, 17 (12), pp.e3000554. ⟨10.1371/journal.pbio.3000554⟩. ⟨inserm-02432807⟩



Record views


Files downloads