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Essential functions of synapsins I and II in synaptic vesicle regulation

Nature volume 375, pages 488–493 (1995)Cite this article

Abstract

SYNAPTIC vesicles are coated by synapsins, phosphoproteins that account for 9% of the vesicle protein1-3. To analyse the functions of these proteins, we have studied knockout mice lacking either synapsin I, synapsin II, or both. Mice lacking synapsins are viable and fertile with no gross anatomical abnormalities, but experience seizures with a frequency proportional to the number of mutant alleles. Synapsin-II and double knockouts, but not synapsin-I knockouts, exhibit decreased post-tetanic potentiation and severe synaptic depression upon repetitive stimulation. Intrinsic synaptic-vesicle membrane proteins, but not peripheral membrane proteins or other synaptic proteins, are slightly decreased in individual knockouts and more severely reduced in double knockouts, as is the number of synaptic vesicles. Thus synapsins are not required for neurite outgrowth, synaptogenesis or the basic mechanics of synaptic vesicle traffic, but are essential for accelerating this traffic during repetitive stimulation. The phenotype of the synapsin knockouts could be explained either by deficient recruitment of synaptic vesicles to the active zone, or by impaired maturation of vesicles at the active zone, both of which could lead to a secondary destabilization of synaptic vesicles.

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Authors and Affiliations

  1. Department of Molecular Genetics, The University of Texas Southwestern Medical School, Dallas, Texas, 75235, USA

    Thomas W. Rosahl, Markus Missler, Joachim Herz & Thomas C. Südhof

  2. Department of Biochemistry, The University of Texas Southwestern Medical School, Dallas, Texas, 75235, USA

    Robert E. Hammer

  3. Howard Hughes Medical Institute, The University of Texas Southwestern Medical School, Dallas, Texas, 75235, USA

    Thomas W. Rosahl, Markus Missler, Robert E. Hammer & Thomas C. Südhof

  4. Departments of Psychiatry and Physiology, Center for Neurobiology and Psychiatry, University of California at San Francisco, San Francisco, California, 94143, USA

    Diane Spillane, David K. Selig & Robert C. Malenka

  5. Zentrum Anatomie, Universität Göttingen, 37075, Göttingen, Germany

    Markus Missler & Joachim R. Wolff

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Rosahl, T., Spillane, D., Missler, M. et al. Essential functions of synapsins I and II in synaptic vesicle regulation. Nature 375, 488–493 (1995). https://doi.org/10.1038/375488a0

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