scholarly journals Acute loss of Cell–Cell Communication Caused by G Protein–coupled Receptors: A Critical Role for c-Src

1998 ◽  
Vol 140 (5) ◽  
pp. 1199-1209 ◽  
Author(s):  
Friso R. Postma ◽  
Trudi Hengeveld ◽  
Jacqueline Alblas ◽  
Ben N.G. Giepmans ◽  
Gerben C.M. Zondag ◽  
...  

Gap junctions mediate cell–cell communication in almost all tissues, but little is known about their regulation by physiological stimuli. Using a novel single-electrode technique, together with dye coupling studies, we show that in cells expressing gap junction protein connexin43, cell–cell communication is rapidly disrupted by G protein–coupled receptor agonists, notably lysophosphatidic acid, thrombin, and neuropeptides. In the continuous presence of agonist, junctional communication fully recovers within 1–2 h of receptor stimulation. In contrast, a desensitization-defective G protein–coupled receptor mediates prolonged uncoupling, indicating that recovery of communication is controlled, at least in part, by receptor desensitization. Agonist-induced gap junction closure consistently follows inositol lipid breakdown and membrane depolarization and coincides with Rho-mediated cytoskeletal remodeling. However, we find that gap junction closure is independent of Ca2+, protein kinase C, mitogen-activated protein kinase, or membrane potential, and requires neither Rho nor Ras activation. Gap junction closure is prevented by tyrphostins, by dominant-negative c-Src, and in Src-deficient cells. Thus, G protein–coupled receptors use a Src tyrosine kinase pathway to transiently inhibit connexin43-based cell–cell communication.

2014 ◽  
Vol 10 (10) ◽  
pp. 2495-2504 ◽  
Author(s):  
Renxiang Yan ◽  
Xiaofeng Wang ◽  
Lanqing Huang ◽  
Jun Lin ◽  
Weiwen Cai ◽  
...  

G protein coupled receptors (GPCRs), also known as seven-transmembrane domain receptors, pass through the cellular membrane seven times and play diverse biological roles in the cells such as signaling, transporting of molecules and cell–cell communication.


Author(s):  
Joël Bockaert ◽  
Sylvie Claeysen ◽  
Carine Bécamel ◽  
Pinloche Sylvie ◽  
Aline Dumuis

2002 ◽  
Vol 278 (1) ◽  
pp. 124-130 ◽  
Author(s):  
Jeanne M. Manganello ◽  
Jin-Sheng Huang ◽  
Tohru Kozasa ◽  
Tatyana A. Voyno-Yasenetskaya ◽  
Guy C. Le Breton

2001 ◽  
Vol 357 (2) ◽  
pp. 587-592 ◽  
Author(s):  
Nickolai O. DULIN ◽  
Sergei N. ORLOV ◽  
Chad M. KITCHEN ◽  
Tatyana A. VOYNO-YASENETSKAYA ◽  
Joseph M. MIANO

A hallmark of cultured smooth muscle cells (SMCs) is the rapid down-regulation of several lineage-restricted genes that define their in vivo differentiated phenotype. Identifying factors that maintain an SMC differentiated phenotype has important implications in understanding the molecular underpinnings governing SMC differentiation and their subversion to an altered phenotype in various disease settings. Here, we show that several G-protein coupled receptors [α-thrombin, lysophosphatidic acid and angiotensin II (AII)] increase the expression of smooth muscle calponin (SM-Calp) in rat and human SMC. The increase in SM-Calp protein appears to be selective for G-protein-coupled receptors as epidermal growth factor was without effect. Studies using AII showed a 30-fold increase in SM-Calp protein, which was dose- and time-dependent and mediated by the angiotensin receptor-1 (AT1 receptor). The increase in SM-Calp protein with AII was attributable to transcriptional activation of SM-Calp based on increases in steady-state SM-Calp mRNA, increases in SM-Calp promoter activity and complete abrogation of protein induction with actinomycin D. To examine the potential role of extracellular signal-regulated kinase (Erk1/2), protein kinase B, p38 mitogen-activated protein kinase and protein kinase C in AII-induced SM-Calp, inhibitors to each of the signalling pathways were used. None of these signalling molecules appears to be crucial for AII-induced SM-Calp expression, although Erk1/2 may be partially involved. These results identify SM-Calp as a target of AII-mediated signalling, and suggest that the SMC response to AII may incorporate a novel activity of SM-Calp.


1998 ◽  
Vol 511 (2) ◽  
pp. 333-346 ◽  
Author(s):  
Francisco Barros ◽  
David Gómez-Varela ◽  
Cristina G. Viloria ◽  
Teresa Palomero ◽  
Teresa Giráldez ◽  
...  

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