Tomosyn2 is required for normal motor performance

Authors: Cornelia J Geerts Jaap J Plomp Bastijn Koopmans Maarten Loos Elizabeth M van der Pijl Martin A van der Valk Matthijs Verhage Alexander J A Groffen

Publish Date: 2014/04/18

Volume: 220, Issue: 4, Pages: 1971-1982

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Abstract

Tomosyn1 STXBP5 is a soluble NSF attachment protein receptor complexbinding protein that inhibits vesicle fusion but the role of tomosyn2 STXBP5L in the mammalian nervous system is still unclear Here we generated tomosyn2 null Tom2KO/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 tomosyn2 supports motor performance by regulation of transmitter release willingness to sustain synaptic strength during highfrequency transmission which makes this gene a candidate for involvement in neuromuscular disordersFor excellent technical support we would like to thank Jurjen Broeke Niels Cornelisse Joost Hoetjes Hilde Hopman Hans Lodder Rolinka van der Loo Chris van der Meer Frank den Oudsten Desiree Schut Sabine Spijker Aafje Vossenaar Ruud Wijnands Joke Wortel at the VU and VUmc as well as staff of the AvL laboratory for Experimental Animal Pathology We thank Annelies van der Laan and Joop Wiegant for excellent help with laser scanning confocal microscopy at the microscopy facility of the Molecular Cell Biology Department of the LUMC This study was supported by the EU Eurospin project HealthF22009241498 Synsys project HealthF22009242167 and CMSB2 project 335

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