UNC-80 and the NCA Ion Channels Contribute to Endocytosis Defects in Synaptojanin Mutants

Autor: Erik M. Jorgensen, Kevin S. Hamming, Sean D. Young, Terrance P. Snutch, Colin Thacker, Shigeki Watanabe, Kim Schuske, Maelle Jospin, Deepa Joshi
Rok vydání: 2007
Předmět:
Zdroj: Current Biology. 17:1595-1600
ISSN: 0960-9822
DOI: 10.1016/j.cub.2007.08.036
Popis: SummarySynaptojanin is a lipid phosphatase required to degrade phosphatidylinositol 4,5 bisphosphate (PIP2) 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 PIP2[2]. To identify proteins that act downstream of PIP2 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.
Databáze: OpenAIRE