Regulation of transient receptor potential canonical channel 1 (TRPC1) by sphingosine 1-phosphate in C2C12 myoblasts and its relevance for a role of mechanotransduction in skeletal muscle differentiation
Autor: | Roberta Squecco, Francesca Bini, Giorgia Luciani, Elisabetta Meacci, Sandra Zecchi-Orlandini, Francesca Sbrana, Flaminia Chellini, Chiara Sassoli, Lucia Formigli, Maria Martinesi, Fabio Francini |
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Rok vydání: | 2009 |
Předmět: |
Patch-Clamp Techniques
Myoblasts Skeletal Biology Microscopy Atomic Force Mechanotransduction Cellular Cell Line TRPC1 Mice chemistry.chemical_compound Transient receptor potential channel Membrane Microdomains Sphingosine medicine Animals Humans Myocyte Sphingosine-1-phosphate RNA Small Interfering Muscle Skeletal Cell Shape TRPC TRPC Cation Channels Myogenesis Skeletal muscle Cell Differentiation Cell Biology Cell biology medicine.anatomical_structure chemistry lipids (amino acids peptides and proteins) Stress Mechanical Lysophospholipids C2C12 Signal Transduction |
Zdroj: | Journal of Cell Science. 122:1322-1333 |
ISSN: | 1477-9137 0021-9533 |
Popis: | Transient receptor potential canonical (TRPC) channels provide cation and Ca2+ entry pathways, which have important regulatory roles in many physio-pathological processes, including muscle dystrophy. However, the mechanisms of activation of these channels remain poorly understood. Using siRNA, we provide the first experimental evidence that TRPC channel 1 (TRPC1), besides acting as a store-operated channel, represents an essential component of stretch-activated channels in C2C12 skeletal myoblasts, as assayed by whole-cell patch-clamp and atomic force microscopic pulling. The channel's activity and stretch-induced Ca2+ influx were modulated by sphingosine 1-phosphate (S1P), a bioactive lipid involved in satellite cell biology and tissue regeneration. We also found that TRPC1 was functionally assembled in lipid rafts, as shown by the fact that cholesterol depletion resulted in the reduction of transmembrane ion current and conductance. Association between TRPC1 and lipid rafts was increased by formation of stress fibres, which was elicited by S1P and abolished by treatment with the actin-disrupting dihydrocytochalasin B, suggesting a role for cytoskeleton in TRPC1 membrane recruitment. Moreover, TRPC1 expression was significantly upregulated during myogenesis, especially in the presence of S1P, implicating a crucial role for TRPC1 in myoblast differentiation. Collectively, these findings may offer new tools for understanding the role of TRPC1 and sphingolipid signalling in skeletal muscle regeneration and provide new therapeutic approaches for skeletal muscle disorders. |
Databáze: | OpenAIRE |
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