Abstract
Multinucleated skeletal muscle fibers synthesize cell surface and secreted oligomeric forms of acetylcholinesterase (AChE) that accumulate at specialized locations on the cell surface, such as sites of nerve-muscle contact. Using allelic variants of the AChE polypeptide chains as genetic markers, we show that nuclei homozygous for either the alpha or beta alleles residing in chimeric myotubes preferentially translate their AChE mRNAs on their respective ERs. These results indicate that the events of transcription, translation, and assembly of this membrane protein are compartmentalized into nuclear domains in multinucleated cells, and provide the structural basis for the possible localized expression and regulation of synaptic components at the neuromuscular junctions of vertebrate skeletal muscle fibers.
Full Text
The Full Text of this article is available as a PDF (1.1 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Brimijoin S. Molecular forms of acetylcholinesterase in brain, nerve and muscle: nature, localization and dynamics. Prog Neurobiol. 1983;21(4):291–322. doi: 10.1016/0301-0082(83)90015-1. [DOI] [PubMed] [Google Scholar]
- Brockman S. K., Usiak M. F., Younkin S. G. Assembly of monomeric acetylcholinesterase into tetrameric and asymmetric forms. J Biol Chem. 1986 Jan 25;261(3):1201–1207. [PubMed] [Google Scholar]
- Bursztajn S., Berman S. A., Gilbert W. Differential expression of acetylcholine receptor mRNA in nuclei of cultured muscle cells. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2928–2932. doi: 10.1073/pnas.86.8.2928. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Couteaux R. Structure of the subsynaptic sarcoplasm in the interfolds of the frog neuromuscular junction. J Neurocytol. 1981 Dec;10(6):947–962. doi: 10.1007/BF01258523. [DOI] [PubMed] [Google Scholar]
- Fernandez-Valle C., Rotundo R. L. Regulation of acetylcholinesterase synthesis and assembly by muscle activity. Effects of tetrodotoxin. J Biol Chem. 1989 Aug 25;264(24):14043–14049. [PubMed] [Google Scholar]
- Fontaine B., Changeux J. P. Localization of nicotinic acetylcholine receptor alpha-subunit transcripts during myogenesis and motor endplate development in the chick. J Cell Biol. 1989 Mar;108(3):1025–1037. doi: 10.1083/jcb.108.3.1025. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fontaine B., Sassoon D., Buckingham M., Changeux J. P. Detection of the nicotinic acetylcholine receptor alpha-subunit mRNA by in situ hybridization at neuromuscular junctions of 15-day-old chick striated muscles. EMBO J. 1988 Mar;7(3):603–609. doi: 10.1002/j.1460-2075.1988.tb02853.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Frair P. M., Peterson A. C. The nuclear-cytoplasmic relationship in 'mosaic' skeletal muscle fibers from mouse chimaeras. Exp Cell Res. 1983 Apr 15;145(1):167–178. doi: 10.1016/s0014-4827(83)80018-4. [DOI] [PubMed] [Google Scholar]
- Frair P. M., Strasberg P. M., Freeman K. B., Peterson A. C. Mitochondrial malic enzyme in mosaic skeletal muscle of mouse chimeras. Biochem Genet. 1979 Aug;17(7-8):693–702. doi: 10.1007/BF00502127. [DOI] [PubMed] [Google Scholar]
- Harris D. A., Falls D. L., Fischbach G. D. Differential activation of myotube nuclei following exposure to an acetylcholine receptor-inducing factor. Nature. 1989 Jan 12;337(6203):173–176. doi: 10.1038/337173a0. [DOI] [PubMed] [Google Scholar]
- Horovitz O., Knaack D., Podleski T. R., Salpeter M. M. Acetylcholine receptor alpha-subunit mRNA is increased by ascorbic acid in cloned L5 muscle cells: Northern blot analysis and in situ hybridization. J Cell Biol. 1989 May;108(5):1823–1832. doi: 10.1083/jcb.108.5.1823. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Merlie J. P., Sanes J. R. Concentration of acetylcholine receptor mRNA in synaptic regions of adult muscle fibres. Nature. 1985 Sep 5;317(6032):66–68. doi: 10.1038/317066a0. [DOI] [PubMed] [Google Scholar]
- Mintz B., Baker W. W. Normal mammalian muscle differentiation and gene control of isocitrate dehydrogenase synthesis. Proc Natl Acad Sci U S A. 1967 Aug;58(2):592–598. doi: 10.1073/pnas.58.2.592. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pavlath G. K., Rich K., Webster S. G., Blau H. M. Localization of muscle gene products in nuclear domains. Nature. 1989 Feb 9;337(6207):570–573. doi: 10.1038/337570a0. [DOI] [PubMed] [Google Scholar]
- Ralston E., Hall Z. W. Transfer of a protein encoded by a single nucleus to nearby nuclei in multinucleated myotubes. Science. 1989 Jun 2;244(4908):1066–1069. doi: 10.1126/science.2543074. [DOI] [PubMed] [Google Scholar]
- Rotundo R. L. Asymmetric acetylcholinesterase is assembled in the Golgi apparatus. Proc Natl Acad Sci U S A. 1984 Jan;81(2):479–483. doi: 10.1073/pnas.81.2.479. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rotundo R. L. Biogenesis of acetylcholinesterase molecular forms in muscle. Evidence for a rapidly turning over, catalytically inactive precursor pool. J Biol Chem. 1988 Dec 25;263(36):19398–19406. [PubMed] [Google Scholar]
- Rotundo R. L., Gomez A. M., Fernandez-Valle C., Randall W. R. Allelic variants of acetylcholinesterase: genetic evidence that all acetylcholinesterase forms in avian nerves and muscles are encoded by a single gene. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7805–7809. doi: 10.1073/pnas.85.20.7805. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schumacher M., Maulet Y., Camp S., Taylor P. Multiple messenger RNA species give rise to the structural diversity in acetylcholinesterase. J Biol Chem. 1988 Dec 15;263(35):18979–18987. [PubMed] [Google Scholar]
- Sikorav J. L., Duval N., Anselmet A., Bon S., Krejci E., Legay C., Osterlund M., Reimund B., Massoulié J. Complex alternative splicing of acetylcholinesterase transcripts in Torpedo electric organ; primary structure of the precursor of the glycolipid-anchored dimeric form. EMBO J. 1988 Oct;7(10):2983–2993. doi: 10.1002/j.1460-2075.1988.tb03161.x. [DOI] [PMC free article] [PubMed] [Google Scholar]