Brain Structure and Function

, Volume 220, Issue 4, pp 1971–1982 | Cite as

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

  • 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. GroffenEmail author
Original Article


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 (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 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.


Neuromuscular junction Release willingness Short-term plasticity STXBP5L Synaptic transmission Tomosyn-2 



For 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 Health-F2-2009-241498, Synsys project Health-F2-2009-242167 and CMSB2 project 3.3.5.

Supplementary material

429_2014_766_MOESM1_ESM.docx (10.7 mb)
Supplementary material 1 (DOCX 10953 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Cornelia J. Geerts
    • 1
  • Jaap J. Plomp
    • 2
  • Bastijn Koopmans
    • 3
  • Maarten Loos
    • 3
  • Elizabeth M. van der Pijl
    • 2
  • Martin A. van der Valk
    • 4
  • Matthijs Verhage
    • 1
    • 5
  • Alexander J. A. Groffen
    • 1
    • 5
    Email author
  1. 1.Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus AmsterdamVU UniversityAmsterdamThe Netherlands
  2. 2.Department of NeurologyLeiden University Medical CentreLeidenThe Netherlands
  3. 3.Sylics (Synaptologics BV)AmsterdamThe Netherlands
  4. 4.Department of Experimental Animal PathologyAntoni van Leeuwenhoek-Netherlands Cancer InstituteAmsterdamThe Netherlands
  5. 5.Department of Clinical GeneticsVU Medical CenterAmsterdamThe Netherlands

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