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.
García
Kelly
K
Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60612, USA.
Nabhani
Thomas
T
García
Jesús
J
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