title: Tomosyn-2 is required for normal motor performance in mice and sustains neurotransmission at motor endplates.
abstract: 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.
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV, Amsterdam, The Netherlands.
authors.forename: Cornelia J
authors.initials: CJ
authors.lastname: Geerts
authors.forename: Jaap J
authors.initials: JJ
authors.lastname: Plomp
authors.forename: Bastijn
authors.initials: B
authors.lastname: Koopmans
authors.forename: Maarten
authors.initials: M
authors.lastname: Loos
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: van der Pijl
authors.forename: Martin A
authors.initials: MA
authors.lastname: van der Valk
authors.forename: Matthijs
authors.initials: M
authors.lastname: Verhage
authors.forename: Alexander J A
authors.initials: AJ
authors.lastname: Groffen
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D001703:Biophysics; D003964:Diaphragm / Q000502:physiology; D004558:Electric Stimulation; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics*; D009045:Motor Endplate / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000166:cytology*; D018408:Patch-Clamp Techniques; D011597:Psychomotor Performance / Q000502:physiology; D050683:R-SNARE Proteins / Q000172:deficiency* / Q000235:genetics; D011950:Receptors, Cholinergic / Q000378:metabolism; D018709:Statistics, Nonparametric; D055366:Synaptic Potentials / Q000235:genetics; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D050683:R-SNARE Proteins; D011950:Receptors, Cholinergic; C492530:STXBP5L protein, mouse