Geerts Cornelia J, Plomp Jaap J, Koopmans Bastijn, Loos Maarten, van der Pijl Elizabeth M, van der Valk Martin A, Verhage Matthijs, Groffen Alexander J A
Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV, Amsterdam, The Netherlands.
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.
突触结合蛋白-1（STXBP5）是一种可溶性N-乙基马来酰胺敏感因子附着蛋白受体复合物结合蛋白，可抑制囊泡融合，但突触结合蛋白-2（STXBP5L）在哺乳动物神经系统中的作用仍不清楚。在此，我们培育出了突触结合蛋白-2基因敲除（Tom2(KO/KO)）小鼠，这些小鼠表现出运动能力受损。这伴随着神经肌肉接头处的突触变化，包括自发乙酰胆碱释放频率增加以及在重复刺激期间肌肉运动终板电位的衰减加快。乙酰胆碱受体的突触后几何排列和功能正常。我们得出结论，突触结合蛋白-2通过调节递质释放意愿来支持运动能力，以在高频传递期间维持突触强度，这使得该基因成为参与神经肌肉疾病的一个候选基因。
