Connexins, Connexons, and Intercellular Communication

Goodenough, Daniel A.; Goliger, Jeffrey A.; Paul, David L.

doi:10.1146/annurev.bi.65.070196.002355

Cited by 1,127 publications

(631 citation statements)

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“…A single intercellular GJ channel consists of two end-to-end orientated hemichannels (termed connexons), each of which transverses one of the two adjoining cell membranes to form an aqueous pore across the lipid bilayer (Fig. 1A) [Goodenough et al, 1996]. The hemichannels are made up by hexamers of tetra-span membrane proteins (termed connexins) with the amino-terminus, and the carboxy-terminus (CT) residing at the cytoplasmic site (Fig.…”

Section: Architecture Of Gap Junctionsmentioning

confidence: 99%

Connexins, cell motility, and the cytoskeleton

Olk

Zoidl

Dermietzel

2009

Cell Motil. Cytoskeleton

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Connexins (Cx) comprise a family of transmembrane proteins, which form intercellular channels between plasma membranes of two adjoining cells, commonly known as gap junctions. Recent reports revealed that Cx proteins interact with diverse cellular components to form a multiprotein complex, which has been termed “Nexus”. Potential interaction partners include proteins such as cytoskeletal proteins, scaffolding proteins, protein kinases and phosphatases. These interactions allow correct subcellular localization of Cxs and functional regulation of gap junction‐mediated intercellular communication. Evidence is accruing that Cxs might have channel‐independent functions, which potentially include regulation of cell migration, cell polarization and growth control. In the current review, we summarize recent knowledge on Cx interactions with cytoskeletal proteins and highlight some aspects of their role in cellular motility. Cell Motil. Cytoskeleton 66: 1000–1016, 2009. © 2009 Wiley‐Liss, Inc.

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Section: Architecture Of Gap Junctionsmentioning

confidence: 99%

Connexins, cell motility, and the cytoskeleton

Olk

Zoidl

Dermietzel

2009

Cell Motil. Cytoskeleton

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“…Gap junctions can consist of proteins from several gene families, and the cell biology of gap junctions has been described in detail in excellent recent reviews (Goodenough et al, 1996;Falk, 2000). Vertebrate gap junctions are commonly thought to consist of connexins Willecke, 2003, 2004).…”

Section: Gap Junctional Signalingmentioning

confidence: 99%

Mathematical model of morphogen electrophoresis through gap junctions

Esser

Smith

Weaver

et al. 2006

Developmental Dynamics

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Gap junctional communication is important for embryonic morphogenesis. However, the factors regulating the spatial properties of small molecule signal flows through gap junctions remain poorly understood. Recent data on gap junctions, ion transporters, and serotonin during left-right patterning suggest a specific model: the net unidirectional transfer of small molecules through long-range gap junctional paths driven by an electrophoretic mechanism. However, this concept has only been discussed qualitatively, and it is not known whether such a mechanism can actually establish a gradient within physiological constraints. We review the existing functional data and develop a mathematical model of the flow of serotonin through the early Xenopus embryo under an electrophoretic force generated by ion pumps. Through computer simulation of this process using realistic parameters, we explored quantitatively the dynamics of morphogen movement through gap junctions, confirming the plausibility of the proposed electrophoretic mechanism, which generates a considerable gradient in the available time frame. The model made several testable predictions and revealed properties of robustness, cellular gradients of serotonin, and the dependence of the gradient on several developmental constants. This work quantitatively supports the plausibility of electrophoretic control of morphogen movement through gap junctions during early left-right patterning. This conceptual framework for modeling gap junctional signaling-an epigenetic patterning mechanism of wide relevance in biological regulation-suggests numerous experimental approaches in other patterning systems.

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“…When connexons from neighboring cells dock together, they form a central pore, which allows for the transfer of ions, metabolites, and messenger molecules p1 kDa in molecular weight. [40][41][42][43] We have demonstrated previously that cells with low gap junction intercellular communication (GJIC) can exhibit good bystander cytotoxicity both in vitro and in vivo. 8,11,44 These studies presented here further examine the role of GJIC in bystander cytotoxicity using two approaches.…”

Section: Introductionmentioning

confidence: 99%

GCV phosphates are transferred between HeLa cells despite lack of bystander cytotoxicity

Gentry

Boucher

et al. 2005

Gene Ther

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The role of gap junctional intercellular communication (GJIC) in bystander killing with herpes simplex virus thymidine kinase (HSV-TK) and ganciclovir (GCV) was evaluated in U251 cells expressing a dominant-negative connexin 43 cDNA (DN14), and in HeLa cells, reportedly devoid of connexin protein. These cell lines both exhibited 0% GJIC when assayed by Lucifer Yellow fluorescent dye microinjection. Bystander cytotoxicity was still apparent in 50:50 cocultures of DN14 and HSV-TK-expressing U251 cells, but not in 50:50 cocultures of HeLa cells. However, the sensitivity of HeLa HSV-TK-expressing cells to GCV decreased nearly 100-fold (IC 90 ¼ 109 mM) when cocultured with bystander cells compared to results in 100% cultures of HSV-TK-expressing cells (IC 90 ¼ 1.2 mM). A more sensitive flow cytometry technique to measure GJIC over 24 h revealed that the DN14 and HeLa cells exhibited detectable levels of communication (29 and 23%, respectively). Transfer of phosphorylated GCV to HeLa bystander cells occurred within 4 h after drug addition, and GCV triphosphate (GCVTP) accumulated to 213784 pmol/10 6 cells after 24 h. In addition, GCVTP levels were decreased in HSV-TK-expressing cells in coculture (867733 pmol/10 6 cells) compared to 100% cultures of HSV-TK-expressing cells (17737188 pmol/10 6 cells). The half-life of GCVTP in the HSV-TK-expressing cells was approximately four times that measured in the bystander cells (12.3 and 3.1 h, respectively). These data suggest that the lack of bystander cytotoxicity in HeLa cocultures is due to low transfer of phosphorylated GCV and a rapid half-life of GCVTP in the bystander cells. Thus, GCV phosphate transfer to non-HSV-TK-expressing bystander cells may mediate either bystander cell killing or sparing of HSV-TK-positive cells, depending upon the cell specific drug metabolism.

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Connexins, Connexons, and Intercellular Communication

Cited by 1,127 publications

References 1 publication

Connexins, cell motility, and the cytoskeleton

Connexins, cell motility, and the cytoskeleton

Mathematical model of morphogen electrophoresis through gap junctions

GCV phosphates are transferred between HeLa cells despite lack of bystander cytotoxicity

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