UNC-80 and the NCA ion channels contribute to endocytosis defects in synaptojanin mutants

Curr Biol. 2007 Sep 18;17(18):1595-600. doi: 10.1016/j.cub.2007.08.036. Epub 2007 Sep 6.

Abstract

Synaptojanin is a lipid phosphatase required to degrade phosphatidylinositol 4,5 bisphosphate (PIP(2)) at cell membranes during synaptic vesicle recycling. Synaptojanin mutants in C. elegans are severely uncoordinated and are depleted of synaptic vesicles, possibly because of accumulation of PIP(2). To identify proteins that act downstream of PIP(2) during endocytosis, we screened for suppressors of synaptojanin mutants in the nematode C. elegans. A class of uncoordinated mutants called "fainters" partially suppress the locomotory, vesicle depletion, and electrophysiological defects in synaptojanin mutants. These suppressor loci include the genes for the NCA ion channels, which are homologs of the vertebrate cation leak channel NALCN, and a novel gene called unc-80. We demonstrate that unc-80 encodes a novel, but highly conserved, neuronal protein required for the proper localization of the NCA-1 and NCA-2 ion channel subunits. These data suggest that activation of the NCA ion channel in synaptojanin mutants leads to defects in recycling of synaptic vesicles.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans / physiology
  • Caenorhabditis elegans Proteins / analysis
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Caenorhabditis elegans Proteins / physiology*
  • Endocytosis / genetics
  • Endocytosis / physiology*
  • Green Fluorescent Proteins / analysis
  • Ion Channels / analysis
  • Ion Channels / metabolism*
  • Models, Genetic
  • Mutation
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology*
  • Neurons / metabolism
  • Phosphoric Monoester Hydrolases / genetics*
  • Synaptic Transmission / genetics
  • Synaptic Vesicles / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Ion Channels
  • NCA-2 protein, C elegans
  • Nerve Tissue Proteins
  • UNC-80 protein, C elegans
  • unc-77 protein, C elegans
  • Green Fluorescent Proteins
  • synaptojanin
  • Phosphoric Monoester Hydrolases