Integrin and cytoskeletal involvement in signalling cell volume changes to glutamine transport in rat skeletal muscle.
1. Muscle glutamine transport is modulated in response to changes in cell volume by a mechanism dependent on active phosphatidylinositol 3-kinase. We investigated the possibility that this mechanism requires interactions between the extracellular matrix (ECM), integrins and the cytoskeleton as components of a mechanochemical transduction system. 2. Using skeletal muscle cells, we studied effects of (a) inactivating integrin-substratum interactions by using integrin-binding peptide GRGDTP with inactive peptide GRGESP as control, and (b) disrupting the cytoskeleton using colchicine or cytochalasin D, on glutamine transport after brief exposure to hypo-osmotic, isosmotic or hyperosmotic medium (170, 300 and 430 mosmol kg-1, respectively). 3. Neither GRGDTP nor GRGESP significantly affected basal glutamine uptake (0.05 mM; 338 +/- 58 pmol min-1 (mg protein)-1) but GRGDTP specifically prevented the increase (71%) and decrease (39%) in glutamine uptake in response to hypo- and hyperosmotic exposure, respectively. 4. Colchicine and cytochalasin D prevented the increase and decrease in glutamine uptake in response to changes in external osmolality. They also increased basal glutamine uptake by 59 +/- 19 and 85 +/- 16%, respectively, in a wortmannin-sensitive manner. 5. These results indicate involvement of ECM-integrin-mediated cell adhesion and the cytoskeleton in mechanochemical transduction of cell volume changes to chemical signals modulating glutamine transport in skeletal muscle. Phosphatidylinositol 3-kinase may function to maintain the mechanotransducer in an active state.
Department of Anatomy and Physiology, University of Dundee, Dundee DD1 4HN, UK. s.y.low@dundee.ac.uk
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D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D048429:Cell Size / Q000502:physiology; D003078:Colchicine / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D016023:Integrins / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D009994:Osmolar Concentration; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D000077191:Wortmannin
D000730:Androstadienes; D016023:Integrins; D019384:Nucleic Acid Synthesis Inhibitors; D009842:Oligopeptides; D010726:Phosphodiesterase Inhibitors; C080493:fibronectin attachment peptide; D005973:Glutamine; D015638:Cytochalasin D; D003078:Colchicine; D000077191:Wortmannin