UNC-80 and the NCA ion channels contribute to endocytosis defects in synaptojanin mutants.
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.
Jospin
Maelle
M
Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, UT 84112-0840, USA.
Watanabe
Shigeki
S
Joshi
Deepa
D
Young
Sean
S
Hamming
Kevin
K
Thacker
Colin
C
Snutch
Terrance P
TP
Jorgensen
Erik M
EM
Schuske
Kim
K
D000818:Animals; D001369:Axons / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D004705:Endocytosis / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000032:analysis; D007473:Ion Channels / Q000032:analysis / Q000378:metabolism*; D008957:Models, Genetic; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D009435:Synaptic Transmission / Q000235:genetics; D013572:Synaptic Vesicles / Q000378:metabolism