QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 16, Issue 11, 5247-5257, November 2005

This Article Full Text Full Text (PDF) All Versions of this Article: E05-05-0415v1 16/11/5247    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by VanSlyke, J. K. Articles by Musil, L. S. Search for Related Content PubMed PubMed Citation Articles by VanSlyke, J. K. Articles by Musil, L. S.

Cytosolic Stress Reduces Degradation of Connexin43 Internalized from the Cell Surface and Enhances Gap Junction Formation and Function

Division of Molecular Medicine, Oregon Health and Science University, Portland, OR 97239

Submitted May 11, 2005; Revised August 11, 2005; Accepted August 19, 2005
Monitoring Editor: Asma Nusrat

The protein constituents of gap junctions, connexins, have a rapid basal rate of degradation even after transport to the cell surface. We have used cell surface biotinylation to label gap junction-unassembled plasma membrane pools of connexin43 (Cx43) and show that their degradation is inhibited by mild hyperthermia, oxidative stress, and proteasome inhibitors. Cytosolic stress does not perturb endocytosis of biotinylated Cx43, but instead it seems to interfere with its targeting and/or transport to the lysosome, possibly by increasing the level of unfolded protein in the cytosol. This allows more Cx43 molecules to recycle to the cell surface, where they are assembled into long-lived, functional gap junctions in otherwise gap junction assembly-inefficient cells. Cytosolic stress also slowed degradation of biotinylated Cx43 in gap junction assembly-efficient normal rat kidney fibroblasts, and reduced the rate at which gap junctions disappeared from cell interfaces under conditions that blocked transport of nascent connexin molecules to the plasma membrane. These data demonstrate that degradation from the cell surface can be down-regulated by physiologically relevant forms of stress. For connexins, this may serve to enhance or preserve gap junction-mediated intercellular communication even under conditions in which protein synthesis and/or intracellular transport are compromised.

Abbreviations used: BFA, brefeldin A; CLQ, chloroquine; Cx43, connexin43; ERAD, endoplasmic reticulum-associated degradation; MesNa, sodium 2-mercaptoethanesulfonate.

Address correspondence to: Linda S. Musil (musill{at}ohsu.edu).

This article has been cited by other articles:

				E. Leithe, A. Kjenseth, S. Sirnes, H. Stenmark, A. Brech, and E. Rivedal Ubiquitylation of the gap junction protein connexin-43 signals its trafficking from early endosomes to lysosomes in a process mediated by Hrs and Tsg101 J. Cell Sci., November 1, 2009; 122(21): 3883 - 3893. [Abstract] [Full Text] [PDF]

				J. K. VanSlyke, C. C. Naus, and L. S. Musil Conformational Maturation and Post-ER Multisubunit Assembly of Gap Junction Proteins Mol. Biol. Cell, May 1, 2009; 20(9): 2451 - 2463. [Abstract] [Full Text] [PDF]

				J. E. Maxson, C. A. Enns, and A.-S. Zhang Processing of hemojuvelin requires retrograde trafficking to the Golgi in HepG2 cells Blood, February 19, 2009; 113(8): 1786 - 1793. [Abstract] [Full Text] [PDF]

				K. A. Schalper, N. Palacios-Prado, M. A. Retamal, K. F. Shoji, A. D. Martinez, and J. C. Saez Connexin Hemichannel Composition Determines the FGF-1-induced Membrane Permeability and Free [Ca2+]i Responses Mol. Biol. Cell, August 1, 2008; 19(8): 3501 - 3513. [Abstract] [Full Text] [PDF]

				A.-S. Zhang, F. Yang, K. Meyer, C. Hernandez, T. Chapman-Arvedson, P. J. Bjorkman, and C. A. Enns Neogenin-mediated Hemojuvelin Shedding Occurs after Hemojuvelin Traffics to the Plasma Membrane J. Biol. Chem., June 20, 2008; 283(25): 17494 - 17502. [Abstract] [Full Text] [PDF]

				J. H.-C. Lin, N. Lou, N. Kang, T. Takano, F. Hu, X. Han, Q. Xu, D. Lovatt, A. Torres, K. Willecke, et al. A Central Role of Connexin 43 in Hypoxic Preconditioning J. Neurosci., January 16, 2008; 28(3): 681 - 695. [Abstract] [Full Text] [PDF]

				S. Mitra, L. Annamalai, S. Chakraborty, K. Johnson, X.-H. Song, S. K. Batra, and P. P. Mehta Androgen-regulated Formation and Degradation of Gap Junctions in Androgen-responsive Human Prostate Cancer Cells Mol. Biol. Cell, December 1, 2006; 17(12): 5400 - 5416. [Abstract] [Full Text] [PDF]

				M. A. Retamal, C. J. Cortes, L. Reuss, M. V. L. Bennett, and J. C. Saez S-nitrosylation and permeation through connexin 43 hemichannels in astrocytes: Induction by oxidant stress and reversal by reducing agents PNAS, March 21, 2006; 103(12): 4475 - 4480. [Abstract] [Full Text] [PDF]