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Desmoglein directs differentiation

Activated EGFR (green) is only found in the bottom undifferentiated layer of wild-type skin cultures (left) but spreads throughout the skin in the absence of Dsg1 (right).

The cell adhesion protein desmoglein 1 (Dsg1) has an extra function in suppressing EGF receptor (EGFR) signaling, helping skin cells differentiate into the different layers of the epidermis, report Getsios, Simpson, et al.

Desmogleins are transmembrane components of desmosomes, which hold epithelial cells together and help them resist mechanical stress by connecting with the intermediate filament cytoskeleton. In a multi-layered epithelium such as the epidermis, different desmogleins are expressed in distinct patterns, and may therefore direct the process by which the different layers are specified.

Getsios and colleagues were particularly interested in Dsg1 because its expression in the skin matches the time and place that undifferentiated skin cells stop dividing and develop into all the other layers of the epidermis. Organotypic cultures made from skin cells lacking Dsg1 failed to differentiate in the more mature layers. Surprisingly, Dsg1 didn't need its adhesive activity to support proper differentiation; nor did it rely on two of its desmosomal partners, plakoglobin and desmocollin 1, to exert its effect.

Dsg1 did, however, need to be at the cell membrane where it promotes skin morphogenesis by inhibiting EGFR signaling. EGFR keeps skin cells in their undifferentiated state, and the team found that this receptor was active throughout Dsg1-deficient organotypic cultures. Blocking EGFR or its downstream kinases Erk1/2 restored normal differentiation to skin cells lacking Dsg1. Author Kathleen Green says this is an important demonstration that transmembrane desmosomal proteins like Dsg1 can have signaling functions distinct from their role in cell adhesion. The next challenge is to determine how the protein interferes with EGFR.

References

Getsios, S., C.L. Simpson, et al. 2009. J. Cell Biol. doi:10.1083/jcb.200809044.[Abstract/Free Full Text]

bshort{at}rockefeller.edu

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Desmoglein 1–dependent suppression of EGFR signaling promotes epidermal differentiation and morphogenesis

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