PXD013003

PXD013003 is an original dataset announced via ProteomeXchange.

Title	Ubiquitin mediated intracellular trafficking is required for Jam-C function
Description	Endothelial cells form a barrier between the components present in the blood and the underlying tissue. Essential to formation of this barrier are junctional complexes present between cells. These complexes are dynamic, tightly regulated and remodel during key physiological processes such as inflammation, angiogenesis and development to allow passage of molecules, cells and movement of endothelial cells. One such junctional protein, Jam-C, is involved in the pathology of a number of inflammatory disease states and its inhibition in vitro and in vivo results in aberrant forms of leukocyte migration, dysregulated angiogenesis and inhibition of cell migration. Intracellular trafficking has been shown to be a general means of regulating the function of junctional proteins but its role in Jam-C function is unclear. Using a combination of receptor mutagenesis, HRP and APEX-2 proximity labelling alongside light and electron microscopy, we here characterise the dynamics and route of Jam-C trafficking. Rather than trafficking with junctional proteins associated with the inflammatory process, Jam-C co-traffics with receptors associated with changes in permeability such as VE-Cadherin, NRP-1 and 2. We show that Jam-C becomes ubiquitylated by the E-3 ligase CBL and that this post translational modification controls the likelihood of its degradation in the lysosomes or its recycling back to the cell surface. Finally, we show that Jam-C trafficking is essential for some of the endothelial functions of Jam-C.
HostingRepository	PRIDE
AnnounceDate	2019-11-06
AnnouncementXML	Submission_2019-11-06_06:45:58.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Vinothini Rajeeve
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-03-06 08:29:12	ID requested
⏵ 1	2019-11-06 06:45:59	announced

Dataset with its publication pending

submitter keyword: Jam-C, LC-MS/MS, proteomics, intracellular trafficking, ubiquitin, endothelial cells

Dr Pedro Cutillas
contact affiliation	Cell Signalling & Proteomics Group, Barts Cancer Institute, Queen Mary University of London, London, UK
contact email	p.cutillas@qmul.ac.uk
lab head
Vinothini Rajeeve
contact affiliation	Centre for Haemato Oncology
contact email	v.rajeeve@qmul.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/11/PXD013003

PRIDE project URI

• PRIDE
  1. PXD013003
     1. Label: PRIDE project
     2. Name: Ubiquitin mediated intracellular trafficking is required for Jam-C function