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Syne proteins anchor muscle nuclei at the neuromuscular junction
- R. Mark Grady*,†,‡,
- Daniel A. Starr‡,§,¶,∥,
- Gail L. Ackerman§,
- Joshua R. Sanes*,∥,**,††, and
- Min Han§,††
- Departments of *Anatomy and Neurobiology and †Pediatrics, Washington University, St. Louis, MO 63110; §Department of Molecular, Cellular, and Developmental Biology and Howard Hughes Medical Institute, University of Colorado, Boulder, CO 80309; ¶Section of Molecular and Cellular Biology and Center for Genetics and Development, University of California, Davis, CA 95616; and **Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138
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Contributed by Joshua R. Sanes, January 27, 2005
Abstract
Vertebrate skeletal muscle fibers contain hundreds of nuclei, of which three to six are functionally specialized and stably anchored beneath the postsynaptic membrane at the neuromuscular junction (NMJ). The mechanisms that localize synaptic nuclei and the roles they play in neuromuscular development are unknown. Syne-1 is concentrated at the nuclear envelope of synaptic nuclei; its Caenorhabditis elegans orthologue ANC-1 functions to tether nuclei to the cytoskeleton. To test the involvement of Syne proteins in nuclear anchoring, we generated transgenic mice overexpressing the conserved C-terminal Klarsicht/ANC-1/Syne homology domain of Syne-1. The transgene acted in a dominant interfering fashion, displacing endogenous Syne-1 from the nuclear envelope. Muscle nuclei failed to aggregate at the NMJ in transgenic mice, demonstrating that localization and positioning of synaptic nuclei require Syne proteins. We then exploited this phenotype to show that synaptic nuclear aggregates are dispensable for maturation of the NMJ.
Footnotes
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↵ ∥ To whom correspondence may be addressed. E-mail: dstarr{at}ucdavis.edu or sanesj{at}mcb.harvard.edu.
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↵ ‡ R.M.G. and D.A.S. contributed equally to this work.
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↵ †† J.R.S. and M.H. contributed equally to this work.
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Author contributions: R.M.G., D.A.S., J.R.S., and M.H. designed research; R.M.G., D.A.S., and G.A. performed research; D.A.S. contributed new reagents/analytic tools; R.M.G. and J.R.S. analyzed data; and R.M.G., D.A.S., and J.R.S. wrote the paper.
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Abbreviations: DNS, dominant negative Syne-1; NMJ, neuromuscular junction; BTX, rhodamine-α-bungarotoxin; AChR, acetylcholine receptor; Pn, postnatal day n; KASH, Klarsicht/ANC-1/Syne homology.
- Copyright © 2005, The National Academy of Sciences
