PXD036646

PXD036646 is an original dataset announced via ProteomeXchange.

Title	Epidermal Stratification Requires Retromer-Mediated Desmoglein-1 Recycling
Description	Sorting transmembrane cargo is essential for tissue development and homeostasis. However, mechanisms of intracellular trafficking in stratified epidermis are poorly understood. Here we identify an interaction between the retromer endosomal trafficking component, VPS35, and the desmosomal cadherin, Desmoglein-1 (Dsg1). Dsg1 is specifically expressed in stratified epidermis and when properly localized on the plasma membrane of basal keratinocytes, promotes stratification. We show that the retromer drives Dsg1 recycling from the endo-lysosomal system to the plasma membrane to support stratification. The retromer-enhancing chaperone, R55, promotes the membrane localization of Dsg1 and a trafficking-deficient mutant associated with a severe inflammatory skin disorder, enhancing its ability to promote stratification. In the absence of Dsg1, retromer association with and expression of the glucose transporter GLUT1 increases, exposing a potential link between Dsg1 deficiency and epidermal metabolism. Our work provides the first evidence for retromer function in epidermal regeneration, identifying it as a potential therapeutic target.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:04:12.591.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Donald Wolfgeher
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-12 05:37:53	ID requested
1	2023-07-24 13:05:37	announced
⏵ 2	2023-11-14 09:04:14	announced	2023-11-14: Updated project metadata.

Hegazy M, Koetsier JL, Huffine AL, Broussard JA, Godsel BM, Cohen-Barak E, Sprecher E, Wolfgeher DJ, Kron SJ, Godsel LM, Green KJ, Epidermal stratification requires retromer-mediated desmoglein-1 recycling. Dev Cell, 57(24):2683-2698.e8(2022) [pubmed]

submitter keyword: desmosome

keratinocyte

epidermal differentiation

skin disease

endosomal trafficking

retromer chaperone

VPS35

SAM syndrome

cadherin

Dsg1

GLUT1

BioID

Dr. Kathleen J. Green
contact affiliation	1) Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA 2) Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA 3) Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois 60611, USA
contact email	kgreen@northwestern.edu
lab head
Donald Wolfgeher
contact affiliation	University of Chicago
contact email	donw@uchicago.edu
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/2023/07/PXD036646

PRIDE project URI

• PRIDE
  1. PXD036646
     1. Label: PRIDE project
     2. Name: Epidermal Stratification Requires Retromer-Mediated Desmoglein-1 Recycling