The calcium channel alpha2/delta1 subunit is involved in extracellular signalling.
The alpha2/delta1 subunit forms part of the dihydropyridine receptor, an essential protein complex for excitation-contraction (EC) coupling in skeletal muscle. Because of the lack of a viable knock-out animal, little is known regarding the role of the alpha2/delta1 subunit in EC coupling or in other cell functions. Interestingly, the alpha2/delta1 appears before the alpha1 subunit in development and contains extracellular conserved domains known to be important in cell signalling and inter-protein interactions. These facts raise the possibility that the alpha2/delta1 subunit performs vital functions not associated with EC coupling. Here, we tested the hypothesis that the alpha2/delta1 subunit is important for interactions of muscle cells with their environment. Using confocal microscopy, we followed the immunolocalization of alpha2/delta1 and alpha1 subunits with age. We found that in 2-day-old myotubes, the alpha2/delta1 subunit concentrated towards the ends of the cells, while the alpha1 subunit clustered near the centre. As myotubes aged (6-12 days), the alpha2/delta1 became evenly distributed along the myotubes and co-localized with alpha1. When the expression of alpha2/delta1 was blocked with siRNA, migration, attachment and spreading of myoblasts were impaired while the L-type calcium current remained unaffected. The results suggest a previously unidentified role of the alpha2/delta1 subunit in skeletal muscle and support the involvement of this protein in extracellular signalling. This new role of the alpha2/delta1 subunit may be crucial for muscle development, muscle repair and at times in which myoblast attachment and migration are fundamental.
Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60612, USA.
Kelly
K
García
Thomas
T
Nabhani
Jesús
J
García
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism*; D051379:Mice; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*
C512066:CACNA2D1 protein, mouse; D015220:Calcium Channels; D034741:RNA, Small Interfering; D002118:Calcium