TY - JOUR
T1 - Synaptotagmin 17 controls neurite outgrowth and synaptic physiology via distinct cellular pathways
AU - Ruhl, David A.
AU - Bomba-Warczak, Ewa
AU - Watson, Emma T.
AU - Bradberry, Mazdak M.
AU - Peterson, Tabitha A.
AU - Basu, Trina
AU - Frelka, Alyssa
AU - Evans, Chantell S.
AU - Briguglio, Joseph S.
AU - Basta, Tamara
AU - Stowell, Michael H.B.
AU - Savas, Jeffrey N.
AU - Roopra, Avtar
AU - Pearce, Robert A.
AU - Piper, Robert C.
AU - Chapman, Edwin R.
N1 - Funding Information:
We would like the thank Anjon Audhya, Meyer Jackson, Matthew Kennedy, Christina Greer, Michael Seibert, and the Chapman laboratory for their comments and support. This study was supported by NIH grants MH061876 and R35NS097362 to E.R.C. D.A.R. was supported by a National Science Foundation Graduate Research Fellowship Program Grant DGE-1256259 and Neuroscience Training Program Grant T32-GM007507. E.R.C. is an Investigator of the Howard Hughes Medical Institute.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-019-11459-4
DO - 10.1038/s41467-019-11459-4
M3 - Article
C2 - 31387992
AN - SCOPUS:85070278506
SN - 2041-1723
VL - 10
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 3532
ER -