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DPM1 modulates desmosomal adhesion and epidermal differentiation through SERPINB5
Maitreyi Rathod1,2, Henriette Franz1, Vivien Beyersdorfer1,2
1Department of Biomedicine, University of Basel, Basel, Switzerland.
The Journal of Cell Biology
|March 13, 2024
Summary
The dolichol phosphate mannosyltransferase (DPM) complex is crucial for skin cell adhesion and differentiation. Loss of DPM1 impairs these processes, affecting epidermal structure and cell connections.
Area of Science:
- Cell Biology
- Dermatology
- Biochemistry
Background:
- Glycosylation is vital for cell-cell adhesion and differentiation.
- The dolichol phosphate mannosyltransferase (DPM) complex regulates glycosylation.
- Its role in desmosomal adhesion and epidermal differentiation requires elucidation.
Purpose of the Study:
- To determine the function of the DPM complex, specifically DPM1, in desmosomal adhesion.
- To investigate the DPM complex's role in epidermal differentiation.
- To identify molecular mechanisms linking DPM1 to these processes.
Main Methods:
- Gene deletion of DPM1 in human keratinocytes.
- 3D organotypic human epidermis models.
- Proteomic analysis to identify interaction partners.
- Western blotting to assess protein phosphorylation.
Main Results:
- DPM1 deletion weakened cell-cell adhesion and disrupted desmosomal component localization.
- Loss of DPM1 impaired epidermal differentiation, causing abnormal cornification and intercellular gaps.
- SERPINB5 was identified as a DPM1-dependent interactor of desmoplakin, reducing its phosphorylation.
Conclusions:
- The DPM complex, via DPM1, plays a novel role in maintaining desmosomal adhesion.
- DPM1 is essential for proper epidermal differentiation and stratification.
- The DPM1-SERPINB5-desmoplakin axis regulates intercellular adhesion and epidermal homeostasis.
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