A single mutation in the acetylcholine receptor δ-subunit causes distinct effects in two types of neuromuscular synapses

Jee Young Park, Meghan Mott, Tory Williams, Hiromi Ikeda, Hua Wen, Michael Linhoff, Fumihito Ono

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Mutations in AChR subunits, expressed as pentamers in neuromuscular junctions (NMJs), cause various types of congenital myasthenic syndromes. In AChR pentamers, the adult ε subunit gradually replaces the embryonic γ subunit as the animal develops. Because of this switch in subunit composition, mutations in specific subunits result in synaptic phenotypes that change with developmental age. However, a mutation in any AChR subunit is considered to affect the NMJs of all muscle fibers equally. Here, we report a zebrafish mutant of the AChR δ subunit that exhibits two distinct NMJ phenotypes specific to two muscle fiber types: slow or fast. Homozygous fish harboring a point mutation in the δ subunit form functional AChRs in slow muscles, whereas receptors in fast muscles are nonfunctional. To test the hypothesis that different subunit compositions in slow and fast muscles underlie distinct phenotypes, we examined the presence of ε/γ subunits in NMJs using specific antibodies. Both wild-type and mutant larvae lacked ε/γ subunits in slow muscle synapses. These findings in zebrafish suggest that some mutations in human congenital myasthenic syndromes may affect slow and fast muscle fibers differently.

Original languageEnglish (US)
Pages (from-to)10211-10218
Number of pages8
JournalJournal of Neuroscience
Volume34
Issue number31
DOIs
StatePublished - Jan 1 2014

Keywords

  • Acetylcholine receptors
  • Neuromuscular diseases
  • Zebrafish

ASJC Scopus subject areas

  • Neuroscience(all)

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