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Plasma Membrane Channels Formed by Connexins: Their Regulation and Functions

Departamento de Ciencias Fisiológicas, Pontificia Universidad Católica de Chile, Santiago, Chile; and Department of Pediatrics, University of Chicago, Chicago, Illinois

Sáez, Juan C., Viviana M. Berthoud, María C. Brañes, Agustín D. Martínez, and Eric C. Beyer. Plasma Membrane Channels Formed by Connexins: Their Regulation and Functions. Physiol Rev 83: 1359-1400, 2003; 10.1152/physrev.00007.2003.—Members of the connexin gene family are integral membrane proteins that form hexamers called connexons. Most cells express two or more connexins. Open connexons found at the nonjunctional plasma membrane connect the cell interior with the extracellular milieu. They have been implicated in physiological functions including paracrine intercellular signaling and in induction of cell death under pathological conditions. Gap junction channels are formed by docking of two connexons and are found at cell-cell appositions. Gap junction channels are responsible for direct intercellular transfer of ions and small molecules including propagation of inositol trisphosphate-dependent calcium waves. They are involved in coordinating the electrical and metabolic responses of heterogeneous cells. New approaches have expanded our knowledge of channel structure and connexin biochemistry (e.g., protein trafficking/assembly, phosphorylation, and interactions with other connexins or other proteins). The physiological role of gap junctions in several tissues has been elucidated by the discovery of mutant connexins associated with genetic diseases and by the generation of mice with targeted ablation of specific connexin genes. The observed phenotypes range from specific tissue dysfunction to embryonic lethality.

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				A. F. Lau c-Src: Bridging the Gap Between Phosphorylation- and Acidification-Induced Gap Junction Channel Closure Sci. Signal., July 5, 2005; 2005(291): pe33 - pe33. [Abstract] [Full Text] [PDF]

				J. Maza, J. D. Sarma, and M. Koval Defining a Minimal Motif Required to Prevent Connexin Oligomerization in the Endoplasmic Reticulum J. Biol. Chem., June 3, 2005; 280(22): 21115 - 21121. [Abstract] [Full Text] [PDF]

				H. S. Kim, E. H. Choi, J. Khan, E. Roilides, A. Francesconi, M. Kasai, T. Sein, R. L. Schaufele, K. Sakurai, C. G. Son, et al. Expression of Genes Encoding Innate Host Defense Molecules in Normal Human Monocytes in Response to Candida albicans Infect. Immun., June 1, 2005; 73(6): 3714 - 3724. [Abstract] [Full Text] [PDF]

				H. Lahlou, M. Fanjul, L. Pradayrol, C. Susini, and S. Pyronnet Restoration of Functional Gap Junctions through Internal Ribosome Entry Site-Dependent Synthesis of Endogenous Connexins in Density-Inhibited Cancer Cells Mol. Cell. Biol., May 15, 2005; 25(10): 4034 - 4045. [Abstract] [Full Text] [PDF]

				Q. Shao, H. Wang, E. McLachlan, G. I.L. Veitch, and D. W. Laird Down-regulation of Cx43 by Retroviral Delivery of Small Interfering RNA Promotes an Aggressive Breast Cancer Cell Phenotype Cancer Res., April 1, 2005; 65(7): 2705 - 2711. [Abstract] [Full Text] [PDF]

				W. Roscoe, G. I. L. Veitch, X.-Q. Gong, E. Pellegrino, D. Bai, E. McLachlan, Q. Shao, G. M. Kidder, and D. W. Laird Oculodentodigital Dysplasia-causing Connexin43 Mutants Are Non-functional and Exhibit Dominant Effects on Wild-type Connexin43 J. Biol. Chem., March 25, 2005; 280(12): 11458 - 11466. [Abstract] [Full Text] [PDF]

				X. Bao, Y. Chen, S. H. Lee, S. C. Lee, L. Reuss, and G. A. Altenberg Membrane Transport Proteins with Complete Replacement of Transmembrane Helices with Polyalanine Sequences Remain Functional J. Biol. Chem., March 11, 2005; 280(10): 8647 - 8650. [Abstract] [Full Text] [PDF]

				B. Levavi-Sivan, C. L. Bloch, M. J. Gutnick, and I. A. Fleidervish Electrotonic Coupling in the Anterior Pituitary of a Teleost Fish Endocrinology, March 1, 2005; 146(3): 1048 - 1052. [Abstract] [Full Text] [PDF]

				X. Lin, J. Gemel, E. C. Beyer, and R. D. Veenstra Dynamic model for ventricular junctional conductance during the cardiac action potential Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1113 - H1123. [Abstract] [Full Text] [PDF]

				D. T. Kurjiaka, S. B. Bender, D. D. Nye, W. B. Wiehler, and D. G. Welsh Hypertension attenuates cell-to-cell communication in hamster retractor muscle feed arteries Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H861 - H870. [Abstract] [Full Text] [PDF]

				M. Vandecasteele, J. Glowinski, and L. Venance Electrical Synapses between Dopaminergic Neurons of the Substantia Nigra Pars Compacta J. Neurosci., January 12, 2005; 25(2): 291 - 298. [Abstract] [Full Text] [PDF]

				R. Araya, D. Eckardt, S. Maxeiner, O. Kruger, M. Theis, K. Willecke, and J. C. Saez Expression of connexins during differentiation and regeneration of skeletal muscle: functional relevance of connexin43 J. Cell Sci., January 1, 2005; 118(1): 27 - 37. [Abstract] [Full Text] [PDF]

				C. Graham and N. L. Simmons Functional organization of the bovine rumen epithelium Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2005; 288(1): R173 - R181. [Abstract] [Full Text] [PDF]

				V. Valiunas, R. Mui, E. McLachlan, G. Valdimarsson, P. R. Brink, and T. W. White Biophysical characterization of zebrafish connexin35 hemichannels Am J Physiol Cell Physiol, December 1, 2004; 287(6): C1596 - C1604. [Abstract] [Full Text] [PDF]

				T. S. Richards, C. A. Dunn, W. G. Carter, M. L. Usui, J. E. Olerud, and P. D. Lampe Protein kinase C spatially and temporally regulates gap junctional communication during human wound repair via phosphorylation of connexin43 on serine368 J. Cell Biol., November 8, 2004; 167(3): 555 - 562. [Abstract] [Full Text] [PDF]