The C-terminal unique region of desmoglein 2 inhibits its internalization via tail-tail interactions

Jing Chen, Oxana E. Nekrasova, Dipal M. Patel, Jodi L. Klessner, Lisa M. Godsel, Jennifer L. Koetsier, Evangeline V. Amargo, Bhushan V. Desai, Kathleen J. Green*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Desmosomal cadherins, desmogleins (Dsgs) and desmocollins, make up the adhesive core of intercellular junctions called desmosomes. A critical determinant of epithelial adhesive strength is the level and organization of desmosomal cadherins on the cell surface. The Dsg subclass of desmosomal cadherins contains a C-terminal unique region (Dsg unique region [DUR]) with unknown function. In this paper, we show that the DUR of Dsg2 stabilized Dsg2 at the cell surface by inhibiting its internalization and promoted strong intercellular adhesion. DUR also facilitated Dsg tail-tail interactions. Forced dimerization of a Dsg2 tail lacking the DUR led to decreased internalization, supporting the conclusion that these two functions of the DUR are mechanistically linked. We also show that a Dsg2 mutant, V977fsX1006, identified in arrhythmogenic right ventricular cardiomyopathy patients, led to a loss of Dsg2 tail self-association and underwent rapid endocytosis in cardiac muscle cells. Our observations illustrate a new mechanism desmosomal cadherins use to control their surface levels, a key factor in determining their adhesion and signaling roles.

Original languageEnglish (US)
Pages (from-to)699-711
Number of pages13
JournalJournal of Cell Biology
Volume199
Issue number4
DOIs
StatePublished - Nov 2012

ASJC Scopus subject areas

  • Cell Biology

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