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Unformatted text preview: THEJOURNALOFCELLBIOLOGY JCB: ARTICLE The Journal of Cell Biology, Vol. 177, No. 5, June 04, 2007 881–891 JCB 881 Introduction Communication between adjacent cells through gap junctions occurs in nearly every tissue and is fundamental to coordinated cell behavior. Gap junctions are composed of connexins, con- sisting of an intracellular N terminus, four transmembrane do- mains, and a cytosolic C-terminal tail. Six connexins oligomerize into a pore-forming connexon, and alignment of two connex- ons in apposing cell membranes forms a gap junction channel. These channels allow direct cell-to-cell diffusion of ions and small molecules ( < 1–2 kD), including nutrients, metabolites, second messengers, and peptides, without transit through the extracellular space (Goodenough et al., 1996; Harris, 2001; Saez et al., 2003). Gap junctions play important roles in normal tissue function and organ development (Reaume et al., 1995; Sohl and Willecke, 2004; Wei et al., 2004) and have been impli- cated in a great diversity of biological processes, notably, elec- trical synchronization of excitable cells, energy metabolism, growth control, wound repair, tumor cell invasion, and antigen cross-presentation (Kwak et al., 2001; Qiu et al., 2003; Mesnil et al., 2005; Oliveira et al., 2005; Neijssen et al., 2005; Bernstein and Morley, 2006; Mori et al., 2006). The importance of gap junctions is highlighted by the discovery that mutations in con- nexins underlie a variety of genetic diseases, including periph- eral neuropathy, skin disorders, and deafness (Gerido and White, 2004; Wei et al., 2004). Connexin43 (Cx43) is the most abundant and best-studied mammalian connexin. Cx43-based gap junctional communica- tion is of a particular interest because it is regulated by both physio- logical and pathophysiological stimuli. In particular, Cx43-based Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate Leonie van Zeijl, 1 Bas Ponsioen, 1,2 Ben N.G. Giepmans, 1 Aafke Ariaens, 1 Friso R. Postma, 1 Péter Várnai, 3 Tamas Balla, 3 Nullin Divecha, 1 Kees Jalink, 2 and Wouter H. Moolenaar 1 1 Division of Cellular Biochemistry, Centre for Biomedical Genetics, and 2 Division of Cell Biology, The Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands 3 Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 C ell–cell communication through connexin43 (Cx43)-based gap junction channels is rapidly inhibited upon activation of various G protein– coupled receptors; however, the mechanism is unknown. We show that Cx43-based cell–cell communication is inhib- ited by depletion of phosphatidylinositol 4,5-bisphosphate (PtdIns[4,5]P 2 ) from the plasma membrane. Knockdown of phospholipase C β 3 (PLC β 3) inhibits PtdIns(4,5)P 2 hydrolysis and keeps Cx43 channels open after recep- tor activation. Using a translocatable 5-phosphatase, we tor activation....
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This note was uploaded on 11/01/2010 for the course PRC 1234 taught by Professor All during the Spring '10 term at HKU.

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