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

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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 (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.

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Acknowledgments

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.

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Authors and Affiliations

  1. Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV, Amsterdam, The Netherlands

    Cornelia J. Geerts, Matthijs Verhage & Alexander J. A. Groffen

  2. Department of Neurology, Leiden University Medical Centre, PO Box 9600, 2300 RC, Leiden, The Netherlands

    Jaap J. Plomp & Elizabeth M. van der Pijl

  3. Sylics (Synaptologics BV), PO Box 71033, 1008 BA, Amsterdam, The Netherlands

    Bastijn Koopmans & Maarten Loos

  4. Department of Experimental Animal Pathology, Antoni van Leeuwenhoek-Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    Martin A. van der Valk

  5. Department of Clinical Genetics, VU Medical Center, 1081 HZ, Amsterdam, The Netherlands

    Matthijs Verhage & Alexander J. A. Groffen

Authors
  1. Cornelia J. Geerts
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  2. Jaap J. Plomp
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  3. Bastijn Koopmans
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  4. Maarten Loos
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  5. Elizabeth M. van der Pijl
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  6. Martin A. van der Valk
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  7. Matthijs Verhage
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  8. Alexander J. A. Groffen
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Corresponding author

Correspondence to Alexander J. A. Groffen.

Additional information

C. J. Geerts and J. J. Plomp contributed equally to this work.

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Geerts, C.J., Plomp, J.J., Koopmans, B. et al. Tomosyn-2 is required for normal motor performance in mice and sustains neurotransmission at motor endplates. Brain Struct Funct 220, 1971–1982 (2015). https://doi.org/10.1007/s00429-014-0766-0

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  • DOI: https://doi.org/10.1007/s00429-014-0766-0

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