Neuronal fusion pore assembly requires membrane cholesterol

Authors

  • Won Jin Cho,

    1. Department of Physiology, Wayne State University, School of Medicine, 5245 Scott Hall, 540 E. Canfield, Detroit, MI 48201, USA
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    • W.J. Cho and A. Jeremic contributed equally to this work.

  • Aleksandar Jeremic,

    1. Department of Physiology, Wayne State University, School of Medicine, 5245 Scott Hall, 540 E. Canfield, Detroit, MI 48201, USA
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    • W.J. Cho and A. Jeremic contributed equally to this work.

    • Present address: Department of Biological Sciences, George Washington University, Washington, DC 20052, USA.

  • Huan Jin,

    1. Department of Biochemistry and Biophysics, University of California SanFrancisco, SanFrancisco, CA 94158, USA
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  • Gang Ren,

    1. Department of Biochemistry and Biophysics, University of California SanFrancisco, SanFrancisco, CA 94158, USA
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  • Bhanu P. Jena

    Corresponding author
    1. Department of Physiology, Wayne State University, School of Medicine, 5245 Scott Hall, 540 E. Canfield, Detroit, MI 48201, USA
      Corresponding author. Tel.: +1 313 577 1532; fax: +1 313 993 4177. bjena@med.wayne.edu
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Corresponding author. Tel.: +1 313 577 1532; fax: +1 313 993 4177. bjena@med.wayne.edu

Abstract

Cholesterol has been proposed to play a critical role in regulating neurotransmitter release and synaptic plasticity. The neuronal porosome/fusion pore, the secretory machinery at the nerve terminal, is a 12–17 nm cup-shaped lipoprotein structure composed of cholesterol and a number of proteins, among them calcium channels, and the t-SNARE proteins Syntaxin-1 and SNAP-25. During neurotransmission, synaptic vesicles dock and fuse at the porosome via interaction of their v-SNARE protein with t-SNAREs at the porosome base. Membrane-associated neuronal t-SNAREs interact in a circular array with liposome-associated neuronal v-SNARE to form the t-/v-SNARE ring complex. The SNARE complex along with calcium is required for the establishment of continuity between opposing bilayers. Here we show that although cholesterol is an integral component of the neuronal porosome and is required for maintaining its physical integrity and function, it has no influence on the conformation of the SNARE ring complex.

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