Dataset Information

Epidermal Stratification Requires Retromer-Mediated Desmoglein-1 Recycling

ABSTRACT: 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.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Keratinocyte

SUBMITTER: Donald Wolfgeher

LAB HEAD: Dr. Kathleen J. Green

PROVIDER: PXD036646 | Pride | 2023-07-24

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20170810_vcs075_17-967_Green_Brendan-Dsg1_ReRun.raw	Raw
	20170810_vcs075_17-967_Green_Brendan-Ecad.raw	Raw
	20170810_vcs075_17-967_Green_Brendan-control.raw	Raw
	220723_Green_BioID_Index.txt	Txt
	220723_Green_BioID_MQ99FDR.xml	Xml

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Publications

Epidermal stratification requires retromer-mediated desmoglein-1 recycling.

Hegazy Marihan M Koetsier Jennifer L JL Huffine Amber L AL Broussard Joshua A JA Godsel Brendan M BM Cohen-Barak Eran E Sprecher Eli E Wolfgeher Donald J DJ Kron Stephen J SJ Godsel Lisa M LM Green Kathleen J KJ

Developmental cell 20221209 24

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 retrom ...[more]

PMID: 36495876

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