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

Katja B. Kostelnik, Amy Barker, Christopher Schultz, Vinothini Rajeeve, Ian J. White, Michel Aurrand-Lions, Sussan Nourshargh, Pedro Cutillas, Thomas D. Nightingale
doi: https://doi.org/10.1101/625913
Katja B. Kostelnik
1Centre for Microvascular Research, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK
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Amy Barker
1Centre for Microvascular Research, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK
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Christopher Schultz
1Centre for Microvascular Research, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK
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Vinothini Rajeeve
2Cell Signalling & Proteomics Group, Barts Cancer Institute, Queen Mary University of London, London, UK
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Ian J. White
3MRC Laboratory of Molecular Cell Biology, University College London, London, UK
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Michel Aurrand-Lions
4Aix Marseille University, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Marseille, France
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Sussan Nourshargh
1Centre for Microvascular Research, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK
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Pedro Cutillas
2Cell Signalling & Proteomics Group, Barts Cancer Institute, Queen Mary University of London, London, UK
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Thomas D. Nightingale
1Centre for Microvascular Research, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK
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  • For correspondence: t.nightingale@qmul.ac.uk
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Abstract

Junctional complexes between endothelial cells form a dynamic barrier that hinder passive diffusion of blood constituents into interstitial tissues. Re-modelling 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, HRP and APEX-2 proximity labelling, alongside light and electron microscopy, to map the intracellular trafficking routes of junctional adhesion molecule-C (Jam-C). We found that Jam-C co-traffics with receptors associated with changes in permeability, such as VE-Cadherin, NRP-1 and 2, but not with junctional proteins associated with the transmigration of leukocytes. Dynamic Jam-C trafficking and degradation is necessary for junctional remodelling during cell migration and angiogenesis. By identifying new trafficking machinery we show that a key point of regulation is the ubiquitylation of Jam-C by the E3 ligase CBL, this controls the rate of recycling versus lysosomal degradation.

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Posted May 02, 2019.
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Dynamic trafficking and turnover of Jam-C is essential for endothelial cell migration
Katja B. Kostelnik, Amy Barker, Christopher Schultz, Vinothini Rajeeve, Ian J. White, Michel Aurrand-Lions, Sussan Nourshargh, Pedro Cutillas, Thomas D. Nightingale
bioRxiv 625913; doi: https://doi.org/10.1101/625913
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Dynamic trafficking and turnover of Jam-C is essential for endothelial cell migration
Katja B. Kostelnik, Amy Barker, Christopher Schultz, Vinothini Rajeeve, Ian J. White, Michel Aurrand-Lions, Sussan Nourshargh, Pedro Cutillas, Thomas D. Nightingale
bioRxiv 625913; doi: https://doi.org/10.1101/625913

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