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Synaptotagmin 17 controls neurite outgrowth and synaptic physiology via distinct cellular pathways

Author

Listed:
  • David A. Ruhl

    (University of Wisconsin)

  • Ewa Bomba-Warczak

    (Northwestern University)

  • Emma T. Watson

    (University of Wisconsin)

  • Mazdak M. Bradberry

    (University of Wisconsin)

  • Tabitha A. Peterson

    (University of Iowa)

  • Trina Basu

    (University of Wisconsin)

  • Alyssa Frelka

    (University of Wisconsin)

  • Chantell S. Evans

    (University of Pennsylvania)

  • Joseph S. Briguglio

    (University of Wisconsin)

  • Tamara Basta

    (University of Colorado at Boulder)

  • Michael H. B. Stowell

    (University of Colorado at Boulder)

  • Jeffrey N. Savas

    (Northwestern University)

  • Avtar Roopra

    (University of Wisconsin)

  • Robert A. Pearce

    (University of Wisconsin)

  • Robert C. Piper

    (University of Iowa)

  • Edwin R. Chapman

    (University of Wisconsin
    Howard Hughes Medical Institute)

Abstract

The synaptotagmin (syt) proteins have been widely studied for their role in regulating fusion of intracellular vesicles with the plasma membrane. Here we report that syt-17, an unusual isoform of unknown function, plays no role in exocytosis, and instead plays multiple roles in intracellular membrane trafficking. Syt-17 is localized to the Golgi complex in hippocampal neurons, where it coordinates import of vesicles from the endoplasmic reticulum to support neurite outgrowth and facilitate axon regrowth after injury. Further, we discovered a second pool of syt-17 on early endosomes in neurites. Loss of syt-17 disrupts endocytic trafficking, resulting in the accumulation of excess postsynaptic AMPA receptors and defective synaptic plasticity. Two distinct pools of syt-17 thus control two crucial, independent membrane trafficking pathways in neurons. Function of syt-17 appears to be one mechanism by which neurons have specialized their secretory and endosomal systems to support the demands of synaptic communication over sprawling neurite arbors.

Suggested Citation

  • David A. Ruhl & Ewa Bomba-Warczak & Emma T. Watson & Mazdak M. Bradberry & Tabitha A. Peterson & Trina Basu & Alyssa Frelka & Chantell S. Evans & Joseph S. Briguglio & Tamara Basta & Michael H. B. Sto, 2019. "Synaptotagmin 17 controls neurite outgrowth and synaptic physiology via distinct cellular pathways," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11459-4
    DOI: 10.1038/s41467-019-11459-4
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