UNC-80 and the NCA Ion Channels Contribute to Endocytosis Defects in Synaptojanin Mutants
2007; Elsevier BV; Volume: 17; Issue: 18 Linguagem: Inglês
10.1016/j.cub.2007.08.036
ISSN1879-0445
AutoresMaëlle Jospin, Shigeki Watanabe, Deepa Joshi, Sean D. Young, Kevin S.C. Hamming, Colin Thacker, Terrance P. Snutch, Erik M. Jørgensen, Kim Schuske,
Tópico(s)Neuroscience and Neural Engineering
ResumoSummary Synaptojanin is a lipid phosphatase required to degrade phosphatidylinositol 4,5 bisphosphate (PIP 2 ) at cell membranes during synaptic vesicle recycling [1, 2]. Synaptojanin mutants in C. elegans are severely uncoordinated and are depleted of synaptic vesicles, possibly because of accumulation of PIP 2 [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 [3], which are homologs of the vertebrate cation leak channel NALCN [4], 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.
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