UNC-16/JIP3 regulates early events in synaptic vesicle protein trafficking via LRK-1/LRRK2 and AP complexes

PLoS Genet. 2017 Nov 16;13(11):e1007100. doi: 10.1371/journal.pgen.1007100. eCollection 2017 Nov.

Abstract

JIP3/UNC-16/dSYD is a MAPK-scaffolding protein with roles in protein trafficking. We show that it is present on the Golgi and is necessary for the polarized distribution of synaptic vesicle proteins (SVPs) and dendritic proteins in neurons. UNC-16 excludes Golgi enzymes from SVP transport carriers and facilitates inclusion of specific SVPs into the same transport carrier. The SVP trafficking roles of UNC-16 are mediated through LRK-1, whose localization to the Golgi is reduced in unc-16 animals. UNC-16, through LRK-1, also enables Golgi-localization of the μ-subunit of the AP-1 complex. AP1 regulates the size but not the composition of SVP transport carriers. Additionally, UNC-16 and LRK-1 through the AP-3 complex regulates the composition but not the size of the SVP transport carrier. These early biogenesis steps are essential for dependence on the synaptic vesicle motor, UNC-104 for axonal transport. Our results show that UNC-16 and its downstream effectors, LRK-1 and the AP complexes function at the Golgi and/or post-Golgi compartments to control early steps of SV biogenesis. The UNC-16 dependent steps of exclusion, inclusion and motor recruitment are critical for polarized distribution of neuronal cargo.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Axonal Transport
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Carrier Proteins / metabolism
  • Dendrites / metabolism
  • Golgi Apparatus / metabolism
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / genetics
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / metabolism
  • Neurons / metabolism
  • Protein Transport / genetics
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Synaptic Vesicles / genetics
  • Synaptic Vesicles / metabolism*
  • Transcription Factor AP-1 / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Transcription Factor AP-1
  • unc-16 protein, C elegans
  • LRK-1 protein, C elegans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Protein-Serine-Threonine Kinases

Grant support

SPK was funded by the Howard Hughes Medical Institute Early Career Scientist Fellowship (http://www.hhmi.org/research/regulation-organelle-transport-axons) and by Department for Science and Technology, (http://www.dst.gov.in); DAE Project 12-R&D-IMS-5.02-0202. BC was provided fellowship by Council of Scientific and Industrial Research (http://www.csir.res.in/home). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.