HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 293/3/C1032    most recent 00011.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science 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 ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Yum, S. W. Articles by Scherer, S. S. Search for Related Content PubMed PubMed Citation Articles by Yum, S. W. Articles by Scherer, S. S.

RECEPTORS AND SIGNAL TRANSDUCTION

Human connexin26 and connexin30 form functional heteromeric and heterotypic channels

¹Section of Neurology, St. Christopher's Hospital for Children, Drexel University College of Medicine, Philadelphia, Pennsylvania; ²Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania; and ³Department of Physiology and Biophysics, State University of New York, Stony Brook, New York

Submitted 9 January 2007 ; accepted in final form 29 June 2007

Mutations in GJB2 and GJB6, the genes that encode the human gap junction proteins connexin26 (Cx26) and connexin30 (Cx30), respectively, cause hearing loss. Cx26 and Cx30 are both expressed in the cochlea, leading to the potential formation of heteromeric hemichannels and heterotypic gap junction channels. To investigate their interactions, we expressed human Cx26 and Cx30 individually or together in HeLa cells. When they were expressed together, Cx26 and Cx30 appeared to interact directly (by their colocalization in gap junction plaques, by coimmunoprecipitation, and by fluorescence resonance energy transfer). Scrape-loading cells that express either Cx26 or Cx30 demonstrated that Cx26 homotypic channels robustly transferred both cationic and anionic tracers, whereas Cx30 homotypic channels transferred cationic but not anionic tracers. Cells expressing both Cx26 and Cx30 also transferred both cationic and anionic tracers by scrape loading, and the rate of calcein (an anionic tracer) transfer was intermediate between their homotypic counterparts by fluorescence recovery after photobleaching. Fluorescence recovery after photobleaching also showed that Cx26 and Cx30 form functional heterotypic channels, allowing the transfer of calcein, which did not pass the homotypic Cx30 channels. Electrophysiological recordings of cell pairs expressing different combinations of Cx26 and/or Cx30 demonstrated unique gating properties of cell pairs expressing both Cx26 and Cx30. These results indicate that Cx26 and Cx30 form functional heteromeric and heterotypic channels, whose biophysical properties and permeabilities are different from their homotypic counterparts.

gap junctions; hearing; fluorescence resonance energy transfer; fluorescence recovery after photobleaching; immunoprecipitation; dye transfer; electrophysiology

This article has been cited by other articles:

				G. Mese, V. Valiunas, P. R. Brink, and T. W. White Connexin26 deafness associated mutations show altered permeability to large cationic molecules Am J Physiol Cell Physiol, October 1, 2008; 295(4): C966 - C974. [Abstract] [Full Text] [PDF]

				G. Kanaporis, G. Mese, L. Valiuniene, T. W. White, P. R. Brink, and V. Valiunas Gap Junction Channels Exhibit Connexin-specific Permeability to Cyclic Nucleotides J. Gen. Physiol., March 31, 2008; 131(4): 293 - 305. [Abstract] [Full Text] [PDF]