Synaptotagmin 17 Controls Neurite Outgrowth and Synaptic Physiology Via Distinct Cellular Pathways

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Aug 8

PMID 31387992

Citations 17

Authors

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 Stowell

Jeffrey N Savas

Avtar Roopra

Robert A Pearce

Robert C Piper

Edwin R Chapman

Affiliations

Soon will be listed here.

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.

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References

Seemann J, Jokitalo E, Pypaert M, Warren G . Matrix proteins can generate the higher order architecture of the Golgi apparatus. Nature. 2000; 407(6807):1022-6. DOI: 10.1038/35039538. View

Pashkova N, Peterson T, Krishnamani V, Breheny P, Stamnes M, Piper R . DEEPN as an Approach for Batch Processing of Yeast 2-Hybrid Interactions. Cell Rep. 2016; 17(1):303-315. PMC: 5594928. DOI: 10.1016/j.celrep.2016.08.095. View

Holt C, Schuman E . The central dogma decentralized: new perspectives on RNA function and local translation in neurons. Neuron. 2013; 80(3):648-57. PMC: 3820025. DOI: 10.1016/j.neuron.2013.10.036. View

Blackmore M, Moore D, Smith R, Goldberg J, Bixby J, Lemmon V . High content screening of cortical neurons identifies novel regulators of axon growth. Mol Cell Neurosci. 2010; 44(1):43-54. PMC: 2890283. DOI: 10.1016/j.mcn.2010.02.002. View

Mastronarde D, Held S . Automated tilt series alignment and tomographic reconstruction in IMOD. J Struct Biol. 2016; 197(2):102-113. PMC: 5247408. DOI: 10.1016/j.jsb.2016.07.011. View

. The ORFeome Collaboration: a genome-scale human ORF-clone resource. Nat Methods. 2016; 13(3):191-2. DOI: 10.1038/nmeth.3776. View

Chapman E . How does synaptotagmin trigger neurotransmitter release?. Annu Rev Biochem. 2008; 77:615-41. DOI: 10.1146/annurev.biochem.77.062005.101135. View

Kwon O, Gainer H, Wray S, Chin H . Identification of a novel protein containing two C2 domains selectively expressed in the rat brain and kidney. FEBS Lett. 1996; 378(2):135-9. DOI: 10.1016/0014-5793(95)01430-6. View

Yeh F, Dong M, Yao J, Tepp W, Lin G, Johnson E . SV2 mediates entry of tetanus neurotoxin into central neurons. PLoS Pathog. 2010; 6(11):e1001207. PMC: 2991259. DOI: 10.1371/journal.ppat.1001207. View

10.

James P, Halladay J, Craig E . Genomic libraries and a host strain designed for highly efficient two-hybrid selection in yeast. Genetics. 1996; 144(4):1425-36. PMC: 1207695. DOI: 10.1093/genetics/144.4.1425. View

11.

Longair M, Baker D, Armstrong J . Simple Neurite Tracer: open source software for reconstruction, visualization and analysis of neuronal processes. Bioinformatics. 2011; 27(17):2453-4. DOI: 10.1093/bioinformatics/btr390. View

12.

Chin H, Choi S, Jang Y, Cho S, Kim H, Lee J . Protein kinase A-dependent phosphorylation of B/K protein. Exp Mol Med. 2006; 38(2):144-52. DOI: 10.1038/emm.2006.18. View

13.

Hirling H . Endosomal trafficking of AMPA-type glutamate receptors. Neuroscience. 2008; 158(1):36-44. DOI: 10.1016/j.neuroscience.2008.02.057. View

14.

Chen D, Gibson E, Kennedy M . A light-triggered protein secretion system. J Cell Biol. 2013; 201(4):631-40. PMC: 3653365. DOI: 10.1083/jcb.201210119. View

15.

Gordon S, Leube R, Cousin M . Synaptophysin is required for synaptobrevin retrieval during synaptic vesicle endocytosis. J Neurosci. 2011; 31(39):14032-6. PMC: 3188371. DOI: 10.1523/JNEUROSCI.3162-11.2011. View

16.

Sharma K, Schmitt S, Bergner C, Tyanova S, Kannaiyan N, Manrique-Hoyos N . Cell type- and brain region-resolved mouse brain proteome. Nat Neurosci. 2015; 18(12):1819-31. PMC: 7116867. DOI: 10.1038/nn.4160. View

17.

Ju W, Choi S, Kwon J, Kwon O, Lee M, Oh S . Expression of brain/kidney protein in Müller cells of rat retina following transient ischemia. Neurosci Lett. 2000; 293(1):53-6. DOI: 10.1016/s0304-3940(00)01492-0. View

18.

Lee H, Kameyama K, Huganir R, Bear M . NMDA induces long-term synaptic depression and dephosphorylation of the GluR1 subunit of AMPA receptors in hippocampus. Neuron. 1998; 21(5):1151-62. DOI: 10.1016/s0896-6273(00)80632-7. View

19.

Han K, Lee U, Jang Y, Cho Y, Jang Y, Hwang I . Differential regulation of B/K protein expression in proximal and distal tubules of rat kidneys with ischemia-reperfusion injury. Am J Physiol Renal Physiol. 2006; 292(1):F100-6. DOI: 10.1152/ajprenal.00009.2006. View

20.

Petchprayoon C, Suwanborirux K, Tanaka J, Yan Y, Sakata T, Marriott G . Fluorescent kabiramides: new probes to quantify actin in vitro and in vivo. Bioconjug Chem. 2005; 16(6):1382-9. DOI: 10.1021/bc050006j. View