Dihydropyridine receptor alpha subunits in normal and dysgenic muscle in vitro: expression of alpha 1 is required for proper targeting and distribution of alpha 2
- PMID: 1659576
- PMCID: PMC2289242
- DOI: 10.1083/jcb.115.5.1345
Dihydropyridine receptor alpha subunits in normal and dysgenic muscle in vitro: expression of alpha 1 is required for proper targeting and distribution of alpha 2
Abstract
We have studied the subcellular distribution of the alpha 1 and alpha 2 subunits of the skeletal muscle dihydropyridine (DHP) receptor with immunofluorescence labeling of normal and dysgenic (mdg) muscle in culture. In normal myotubes both alpha subunits were localized in clusters associated with the T-tubule membranes of longitudinally as well as transversely oriented T-tubules. The DHP receptor-rich domains may represent the sites where triad junctions with the sarcoplasmic reticulum are being formed. In cultures from dysgenic muscle the alpha 1 subunit was undetectable and the distribution patterns of the alpha 2 subunit were abnormal. The alpha subunit did not form clusters nor was it discretely localized in the T-tubule system. Instead, alpha 2 was found diffusely distributed in parts of the T-system, in structures in the perinuclear region and in the plasma membrane. These results suggest that an interaction between the two alpha subunits is required for the normal distribution of the alpha 2 subunit in the T-tubule membranes. Spontaneous fusion of normal non-muscle cells with dysgenic myotubes resulted in a regional expression of the alpha 1 polypeptide near the foreign nuclei, thus defining the nuclear domain of a T-tubule membrane protein in multi-nucleated muscle cells. Furthermore, the normal intracellular distribution of the alpha 2 polypeptide was restored in domains containing a foreign "rescue" nucleus; this supports the idea that direct interactions between the DHP receptor alpha 1 and alpha 2 subunits are involved in the organization of the junctional T-tubule membranes.
Similar articles
-
Triad formation: organization and function of the sarcoplasmic reticulum calcium release channel and triadin in normal and dysgenic muscle in vitro.J Cell Biol. 1993 Dec;123(5):1161-74. doi: 10.1083/jcb.123.5.1161. J Cell Biol. 1993. PMID: 8245124 Free PMC article.
-
Localization of the alpha 1 and alpha 2 subunits of the dihydropyridine receptor and ankyrin in skeletal muscle triads.Neuron. 1990 Sep;5(3):339-51. doi: 10.1016/0896-6273(90)90170-k. Neuron. 1990. PMID: 2169270
-
Formation of triads without the dihydropyridine receptor alpha subunits in cell lines from dysgenic skeletal muscle.J Cell Biol. 1996 Jul;134(2):375-87. doi: 10.1083/jcb.134.2.375. J Cell Biol. 1996. PMID: 8707823 Free PMC article.
-
Biogenesis of transverse tubules and triads: immunolocalization of the 1,4-dihydropyridine receptor, TS28, and the ryanodine receptor in rabbit skeletal muscle developing in situ.J Cell Biol. 1991 Jan;112(2):289-301. doi: 10.1083/jcb.112.2.289. J Cell Biol. 1991. PMID: 1846372 Free PMC article.
-
Muscular dysgenesis: a model system for studying skeletal muscle development.FASEB J. 1990 Jul;4(10):2798-808. doi: 10.1096/fasebj.4.10.2197156. FASEB J. 1990. PMID: 2197156 Review.
Cited by
-
Computer modeling of siRNA knockdown effects indicates an essential role of the Ca2+ channel alpha2delta-1 subunit in cardiac excitation-contraction coupling.Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):11091-6. doi: 10.1073/pnas.0700577104. Epub 2007 Jun 11. Proc Natl Acad Sci U S A. 2007. PMID: 17563358 Free PMC article.
-
The structure of Ca(2+) release units in arthropod body muscle indicates an indirect mechanism for excitation-contraction coupling.Biophys J. 2002 Nov;83(5):2742-53. doi: 10.1016/S0006-3495(02)75284-3. Biophys J. 2002. PMID: 12414707 Free PMC article.
-
Cored in the act: the use of models to understand core myopathies.Dis Model Mech. 2019 Dec 19;12(12):dmm041368. doi: 10.1242/dmm.041368. Dis Model Mech. 2019. PMID: 31874912 Free PMC article. Review.
-
Caveolin-1(-/-)- and caveolin-2(-/-)-deficient mice both display numerous skeletal muscle abnormalities, with tubular aggregate formation.Am J Pathol. 2007 Jan;170(1):316-33. doi: 10.2353/ajpath.2007.060687. Am J Pathol. 2007. PMID: 17200204 Free PMC article.
-
Absence of the beta subunit (cchb1) of the skeletal muscle dihydropyridine receptor alters expression of the alpha 1 subunit and eliminates excitation-contraction coupling.Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13961-6. doi: 10.1073/pnas.93.24.13961. Proc Natl Acad Sci U S A. 1996. PMID: 8943043 Free PMC article.