Tomosyn-2 is required for normal motor performance in mice and sustains neurotransmission at motor endplates

Brain Struct Funct. 2015 Jul;220(4):1971-82. doi: 10.1007/s00429-014-0766-0. Epub 2014 Apr 18.


Tomosyn-1 (STXBP5) is a soluble NSF attachment protein receptor complex-binding protein that inhibits vesicle fusion, but the role of tomosyn-2 (STXBP5L) in the mammalian nervous system is still unclear. Here we generated tomosyn-2 null (Tom2(KO/KO)) mice, which showed impaired motor performance. This was accompanied by synaptic changes at the neuromuscular junction, including enhanced spontaneous acetylcholine release frequency and faster depression of muscle motor endplate potentials during repetitive stimulation. The postsynaptic geometric arrangement and function of acetylcholine receptors were normal. We conclude that tomosyn-2 supports motor performance by regulation of transmitter release willingness to sustain synaptic strength during high-frequency transmission, which makes this gene a candidate for involvement in neuromuscular disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport
  • Animals
  • Biophysics
  • Diaphragm / physiology
  • Electric Stimulation
  • Embryo, Mammalian
  • Gene Expression Regulation / genetics
  • Hippocampus / cytology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity / genetics*
  • Motor Endplate / metabolism*
  • Neuromuscular Junction / cytology*
  • Patch-Clamp Techniques
  • Psychomotor Performance / physiology
  • R-SNARE Proteins / deficiency*
  • R-SNARE Proteins / genetics
  • Receptors, Cholinergic / metabolism
  • Statistics, Nonparametric
  • Synaptic Potentials / genetics
  • Synaptic Transmission / physiology*


  • Adaptor Proteins, Vesicular Transport
  • R-SNARE Proteins
  • Receptors, Cholinergic
  • STXBP5L protein, mouse