Expression of connexins during differentiation and regeneration of skeletal muscle: functional relevance of connexin43

Araya, Roberto; Eckardt, Dominik; Maxeiner, Stephan; Krüger, Olaf; Theis, Martin; Willecke, Klaus; Sáez, Juan C.

doi:10.1242/jcs.01553

Cited by 98 publications

(114 citation statements)

References 79 publications

(83 reference statements)

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“…Cx43 protein is the predominant connexin in skeletal muscle and its involvement in myogenesis and muscle regeneration have been well documented [6,[23][24][25]. We have demonstrated that expression levels of Cx43 are greatly enhanced by S1P in C2C12 skeletal myoblasts and provided the basis for considering the gap junctional protein as an intracellular target of the pro-myogenic action of the sphingolipid [6].…”

Section: Introductionmentioning

confidence: 63%

Functional interaction between TRPC1 channel and connexin-43 protein: a novel pathway underlying S1P action on skeletal myogenesis

Meacci

Bini

Sassoli

et al. 2010

Cell. Mol. Life Sci.

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We recently demonstrated that skeletal muscle differentiation induced by sphingosine 1-phosphate (S1P) requires gap junctions and transient receptor potential canonical 1 (TRPC1) channels. Here, we searched for the signaling pathway linking the channel activity with Cx43 expression/function, investigating the involvement of the Ca 2? -sensitive protease, m-calpain, and its targets in S1P-induced C2C12 myoblast differentiation. Gene silencing and pharmacological inhibition of TRPC1 significantly reduced Cx43 up-regulation and Cx43/cytoskeletal interaction elicited by S1P. TRPC1-dependent functions were also required for the transient increase of m-calpain activity/expression and the subsequent decrease of PKCa levels. Remarkably, Cx43 expression in S1P-treated myoblasts was reduced by m-calpain-siRNA and enhanced by pharmacological inhibition of classical PKCs, stressing the relevance for calpain/PKCa axis in Cx43 protein remodeling. The contribution of this pathway in myogenesis was also investigated. In conclusion, these findings provide novel mechanisms by which S1P regulates myoblast differentiation and offer interesting therapeutic options to improve skeletal muscle regeneration.

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Section: Introductionmentioning

confidence: 63%

Functional interaction between TRPC1 channel and connexin-43 protein: a novel pathway underlying S1P action on skeletal myogenesis

Meacci

Bini

Sassoli

et al. 2010

Cell. Mol. Life Sci.

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“…Our in vivo and in vitro results indicate that KCs express at least Cx43 but they might also express other Cx types as other macrophagic cells do. For example, monocyte/ macrophages also express Cx37 (21) and Cx45 (19) and microglia also express Cx36 (22).…”

Section: Discussionmentioning

confidence: 99%

“…To rule out the possibility that microinjected LY might be released to the extracellular space and then incorporated to neighboring cells via organic anion transporters or pannexin1 hemichannels activated by a rise in intracellular free Ca 2+ concentration through P2X channels (17), dye coupling assays were performed either in the presence of probenecid (18), an organic anion transporter blocker, or oxidized ATP, a P2X channel blocker (19). The dye transfer of LY to neighboring cells after microinjection of LY into a single cell was not altered by the presence of 50 μM probenecid or 100 μM oxidized ATP (for each compound, n = 4, Fig.…”

Section: Treatment With Lps Plus Ifn-γ Induces Intercellular Communicmentioning

confidence: 99%

Inflammatory conditions induce gap junctional communication between rat Kupffer cells both in vivo and in vitro

Eugenín

González

Sánchez

et al. 2007

Cellular Immunology

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Connexin43 (Cx43), a gap junction protein subunit, has been previously detected in Kupffer cells (KCs) during liver inflammation, however, KCs phagocytose cell debris that may include Cx43 protein, which could explain the detection of Cx43 in KCs. We determined that KCs express Cx43 and form gap junctions both in vivo and in vitro. In liver sections of animals treated with LPS, Cx43 was detected at ED2+ cells interfaces, indicating formation of GJ between KCs in vivo. In vitro, unstimulated KCs cultures did not form functional GJs, and expressed low levels of Cx43 that showed a diffuse intracellular distribution. In contrast, KCs treated with LPS plus IFN-γ, expressed a greater amount of Cx43 at both the, protein and mRNA levels, and showed Cx43 at cell-cell contacts associated with higher dye coupling. In conclusion, activation of KCs in vivo or in vitro resulted in enhanced Cx43 expression levels and formation of GJ that might play relevant roles during liver inflammation.

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“…Such morphogenetic control could be exerted by GJC-mediated changes in differentiation (Zhang et al, 2002;Araya et al, 2003Araya et al, , 2005Gu et al, 2003;Hirschi et al, 2003), proliferation (Paraguassu-Braga et al, 2003;Pearson et al, 2005), or cell migration (Minkoff et al, 1997;Huang et al, 1998;Lecanda et al, 2000;OviedoOrta et al, 2002;Kjaer et al, 2004). To integrate GJC-dependent signals into the systems that control complex morphology, it is necessary to understand the factors regulating spatial flows of signals through gap junctions.…”

Section: Behavior Is Dependent Upon Gap Junction (Gj) -Mediated Signalsmentioning

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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Expression of connexins during differentiation and regeneration of skeletal muscle: functional relevance of connexin43

Cited by 98 publications

References 79 publications

Functional interaction between TRPC1 channel and connexin-43 protein: a novel pathway underlying S1P action on skeletal myogenesis

Functional interaction between TRPC1 channel and connexin-43 protein: a novel pathway underlying S1P action on skeletal myogenesis

Inflammatory conditions induce gap junctional communication between rat Kupffer cells both in vivo and in vitro

Mathematical model of morphogen electrophoresis through gap junctions

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