Desmosomal Cadherin Binding Domains of Plakoglobin

doi:10.1074/jbc.271.18.10904

Desmosomal Cadherin Binding Domains of Plakoglobin (*)

From the (1)Department of Cell Biology, Ronald O. Perelman Department of Dermatology and Kaplan Cancer Center, New York University Medical Center, New York, New York 10016 and the
(2)Memorial Sloan Kettering Cancer Center, New York, New York 10021

^§ To whom correspondence should be addressed:
Dept. of Cell Biology, Ronald O. Perelman Dept. of Dermatology and Kaplan Cancer Center, New York University Medical Center, 550 First Ave., New York, NY 10016.
Tel.: 212-263-8715/6915; Fax: 212-263-8139.

Abstract

Plakoglobin is a major component of both desmosomes and adherens junctions. At these sites it binds to the cytoplasmic domains of cadherin cell-cell adhesion proteins and regulates their adhesive and cytoskeletal binding functions. Plakoglobin also forms distinct cytosolic protein complexes that function in pathways of tumor suppression and cell fate determination. Recent studies in Xenopus suggest that cadherins inhibit the signaling functions of plakoglobin presumably by sequestering this protein at the membrane and depleting its cytosolic pool. To understand the reciprocal regulation between desmosomal cadherins (desmoglein and desmocollin) and plakoglobin, we have sought to identify the binding domains involved in the formation of these protein complexes. Plakoglobin comprises 13 central repeats flanked by amino-terminal and carboxyl-terminal domains. Our results show that repeats 1-4 are involved in binding desmoglein-1. In contrast, the interaction of plakoglobin with desmocollin-1a is sensitive to deletion of either end of the central repeat domain. The binding sites for two adherens junction components, α-catenin and classical cadherins, overlap these sites. Competition among these proteins for binding sites on plakoglobin may therefore account for the distinct composition of adherens junctions and desmosomes.

Footnotes

↵* This work was supported by National Institutes of Health Grants GM47429 (to P. C.) and GM37432 (to B. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹ The abbreviations used are:

Dsg

desmoglein

Dsc

desmocollin

GB

GenBank

PCR

polymerase chain reaction

PECAM

platelet-endothelial cell adhesion molecule

PP2A

protein phosphatase 2A

TX-100

Triton X-100

SD

synthetic media + 2% dextrose.
↵²The cDNA sequences referred to in the text are: bovine desmoglein 1 GB, X57784; bovine desmocollin 1a GB, X56967; bovine desmocollin 1b GB, M61750; Human plakoglobin GB, Z68228; Xenopus α catenin GB, U47624.
- Received February 5, 1996.
- Revision received February 27, 1996.