Syne proteins anchor muscle nuclei at the neuromuscular junction

R. Mark Grady, Daniel A. Starr, Gail L. Ackerman, Joshua R. Sanes, Min Han

Research output: Contribution to journalArticlepeer-review

162 Scopus citations

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.

Original languageEnglish
Pages (from-to)4359-4364
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number12
DOIs
StatePublished - Mar 22 2005

Keywords

  • Acetylcholine receptors
  • Nuclear aggregates
  • Nuclear envelope
  • Synaptic nuclei
  • Syne-1

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