A Single Mutation in the Acetylcholine Receptor delta-Subunit Causes Distinct Effects in Two Types of Neuromuscular Synapses

作者：Park Jee Young; Mott Meghan; Williams Tory; Ikeda Hiromi; Wen Hua; Linhoff Michael; Ono Fumihito^*

来源：Journal of Neuroscience, 2014, 34(31): 10211-10218.

DOI：10.1523/JNEUROSCI.0426-14.2014

• acetylcholine receptors
• neuromuscular diseases
• zebrafish

Mutations in AChR subunits, expressed as pentamers in neuromuscular junctions (NMJs), cause various types of congenital myasthenic syndromes. In AChR pentamers, the adult epsilon subunit gradually replaces the embryonic gamma 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 delta subunit that exhibits two distinct NMJ phenotypes specific to two muscle fiber types: slow or fast. Homozygous fish harboring a point mutation in the delta 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 epsilon/gamma subunits in NMJs using specific antibodies. Both wild-type and mutant larvae lacked epsilon/gamma 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.

• 出版日期2014-7-30
• 单位NIH