ERp29 Restricts Connexin43 Oligomerization in the Endoplasmic Reticulum

• Type of Material: Article
• Authors: Shamie Das, Emory University; Tekla D. Smith, Emory University; Jayasri Das Sarma, Indian Institute of Science Education and Research; Jeffrey D. Ritzenthaler, Emory University; Jose Maza, Emory University; Benjamin E. Kaplan, Emory University; Leslie A. Cunningham, Emory University; Laurence Suaud, University of Pennsylvania; Michael J. Hubbard, University of Melbourne; Ronald C. Rubenstein, University of Pennsylvania; Michael H Koval, Emory University
• Language: English
• Date: 2009-05-15
• Publisher: The American Society for Cell Biology
• Publication Version: Final Published Version
• Copyright Statement: © 2009 by The American Society for Cell Biology
• Final Published Version (URL): http://www.molbiolcell.org/content/20/10/2593
• Title of Journal or Parent Work: Molecular Biology of the Cell
• Volume: 20
• Issue: 10
• Start Page: 2593
• End Page: 2604
• Grant/Funding Information: This work was supported by National Institutes of Health grants GM-61012, HL-083120, AA-013757 (to M. K.), DK-58046 (to R.C.R.), and AA-013528 (to L.A.C.); the University Research Committee of Emory University (to M. K.); and the American Heart Association (to L. S.). R.C.R. was an Established Investigator of the American Heart Association. M. H. was supported by a Professorial Fellowship from the Melbourne Research Unit for Facial Disorders.
• Research Categories: Biology, Cell

Abstract

Connexin43 (Cx43) is a gap junction protein that forms multimeric channels that enable intercellular communication through the direct transfer of signals and metabolites. Although most multimeric protein complexes form in the endoplasmic reticulum (ER), Cx43 seems to exit from the ER as monomers and subsequently oligomerizes in the Golgi complex. This suggests that one or more protein chaperones inhibit premature Cx43 oligomerization in the ER. Here, we provide evidence that an ER-localized, 29-kDa thioredoxin-family protein (ERp29) regulates Cx43 trafficking and function. Interfering with ERp29 function destabilized monomeric Cx43 oligomerization in the ER, caused increased Cx43 accumulation in the Golgi apparatus, reduced transport of Cx43 to the plasma membrane, and inhibited gap junctional communication. ERp29 also formed a specific complex with monomeric Cx43. Together, this supports a new role for ERp29 as a chaperone that helps stabilize monomeric Cx43 to enable oligomerization to occur in the Golgi apparatus.