Proteomics

Dataset Information

0

The Skin Barrier Defects Caused by Keratinocyte-Specific Deletion of ADAM17 or EGFR are Based on Highly Similar Proteome and Degradome Alterations


ABSTRACT: ADAM17 and EGFR are essential key players for epidermal integrity. Keratinocyte-specific deletion of ADAM17 in mice results in pronounced alterations in terminal differentiation of keratinocytes leading to severe epidermal barrier defects with enhanced transepidermal water loss. Thereby, mice deficient for ADAM17 in keratinocytes phenocopy mice with a keratinocyte-specific deletion of EGFR, highlighting the role of ADAM17 as a “ligand sheddase”, as it sheds membrane bound EGFR ligands from the cell surface and finally modulates EGFR signaling. In this study we aim for the first proteomic / degradomic approach to characterize the disruption of the ADAM17-EGFR signaling axis and its consequences for epidermal barrier formation. Proteomic profiling of the epidermal proteome of mice deficient for either ADAM17 or EGFR in keratinocytes at postnatal days 3 and 10 revealed highly similar protein alterations for ADAM17 and EGFR deficiency. These include massive proteome alterations of structural and regulatory components important for barrier formation, like transglutaminases, involucrin, S100 protein family members and S100 fused-type proteins, such as filaggrin, filaggrin-2 and hornerin. Cleavage site analysis using TAILS reveals, among other ADAM17 dependent cleavage sites, increased proteolytic processing of S100 fused-type proteins, including filaggrin-2. Alterations in proteolytic processing are supported by altered protein abundance of numerous proteases upon keratinocyte-specific Adam17 or Egfr deletion, among them kallikreins, cathepsins and their inhibitors. In addition, N-terminal proteomics indicated usage of alternative translation start sites. This study highlights the essential role of proteolytic processing for maintenance of a functional epidermal barrier. Furthermore it suggests that most defects in formation of the postnatal epidermal barrier upon keratinocyte-specific ADAM17 deletion are mediated via EGFR.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Mus musculus  

TISSUE(S): Skin

DISEASE(S): Not Available

SUBMITTER: Stefan Tholen  

LAB HEAD: Oliver Schilling

PROVIDER: PXD002597 | Pride | 2016-04-20

REPOSITORIES: pride

altmetric image

Publications

Skin Barrier Defects Caused by Keratinocyte-Specific Deletion of ADAM17 or EGFR Are Based on Highly Similar Proteome and Degradome Alterations.

Tholen Stefan S   Wolf Cristina C   Mayer Bettina B   Knopf Julia D JD   Löffek Stefanie S   Qian Yawen Y   Kizhakkedathu Jayachandran N JN   Biniossek Martin L ML   Franzke Claus-Werner CW   Schilling Oliver O  

Journal of proteome research 20160421 5


Keratinocyte-specific deletion of ADAM17 in mice impairs terminal differentiation of keratinocytes leading to severe epidermal barrier defects. Mice deficient for ADAM17 in keratinocytes phenocopy mice with a keratinocyte-specific deletion of epidermal growth factor receptor (EGFR), which highlights the role of ADAM17 as a "ligand sheddase" of EGFR ligands. In this study, we aim for the first proteomic/degradomic approach to characterize the disruption of the ADAM17-EGFR signaling axis and its c  ...[more]

Similar Datasets

2012-06-20 | E-GEOD-38830 | ArrayExpress
2012-10-19 | E-GEOD-41680 | ArrayExpress
2012-09-24 | E-GEOD-38039 | ArrayExpress
2013-08-09 | E-GEOD-40368 | ArrayExpress
2016-07-31 | E-GEOD-74407 | ArrayExpress
2015-09-14 | E-GEOD-72468 | ArrayExpress
2009-08-12 | E-GEOD-12111 | ArrayExpress
| GSE12111 | GEO
2015-07-31 | E-GEOD-68725 | ArrayExpress
2015-07-31 | E-GEOD-68723 | ArrayExpress