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

Maelle Jospin; Shigeki Watanabe; Deepa Joshi; Sean Young; Kevin Hamming; Colin Thacker; Terrance P. Snutch; Erik M. Jorgensen; Kim Schuske

doi:10.1016/j.cub.2007.08.036

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

Maelle Jospin, Shigeki Watanabe, Deepa Joshi, Sean Young, Kevin Hamming, Colin Thacker, Terrance P. Snutch, Erik M. Jorgensen, Kim Schuske

Research output: Contribution to journal › Article › peer-review

59 Scopus citations

Abstract

Synaptojanin 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.

Original language	English (US)
Pages (from-to)	1595-1600
Number of pages	6
Journal	Current Biology
Volume	17
Issue number	18
DOIs	https://doi.org/10.1016/j.cub.2007.08.036
State	Published - Sep 18 2007
Externally published	Yes

Keywords

CELLBIO
MOLNEURO

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology
General Agricultural and Biological Sciences

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10.1016/j.cub.2007.08.036

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@article{72ccad02782b46fca169d7a4d9c0ddf6,

title = "UNC-80 and the NCA Ion Channels Contribute to Endocytosis Defects in Synaptojanin Mutants",

abstract = "Synaptojanin 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.",

keywords = "CELLBIO, MOLNEURO",

author = "Maelle Jospin and Shigeki Watanabe and Deepa Joshi and Sean Young and Kevin Hamming and Colin Thacker and Snutch, {Terrance P.} and Jorgensen, {Erik M.} and Kim Schuske",

note = "Funding Information: We would like to thank M. Zhen for the nca-1 nca-2 unc-80 strain and for sharing unpublished data, P. Morgan for sharing unpublished data, J. Pierce-Shimomura for sharing unc-80 mapping data, M. Alion for unc-80(ox330) and unc-80(ox329), G. Hollopeter for the Punc-17:mCherry strain, M. Gu for the GFP-tagged synaptotagmin strain, B. Grant, K. Sato, and M. Gu for the GFP-tagged clathrin strain, the C. elegans Genome Center for strains, and W. Davis for critical reading of the manuscript. Additionally, we would like to thank J. Weis, N. Jorgensen, and D. Lewis for technical assistance. The research was funded by grants from the National Institutes of Health (NS48391 to K.S., NS034307 to E.M.J) and from the Lowe Syndrome Association and the Lowe Syndrome Trust to K.S. and E.M.J. E.M.J. is an Investigator of the Howard Hughes Medical Institute, T.P.S. is supported by an operating grant from the Canadian Institutes for Health Research and a Canada Research Chair, and M.J. is supported by a long-term fellowship from Human Frontier Science Program. ",

year = "2007",

month = sep,

day = "18",

doi = "10.1016/j.cub.2007.08.036",

language = "English (US)",

volume = "17",

pages = "1595--1600",

journal = "Current Biology",

issn = "0960-9822",

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T1 - UNC-80 and the NCA Ion Channels Contribute to Endocytosis Defects in Synaptojanin Mutants

AU - Jospin, Maelle

AU - Watanabe, Shigeki

AU - Joshi, Deepa

AU - Young, Sean

AU - Hamming, Kevin

AU - Thacker, Colin

AU - Snutch, Terrance P.

AU - Jorgensen, Erik M.

AU - Schuske, Kim

N1 - Funding Information: We would like to thank M. Zhen for the nca-1 nca-2 unc-80 strain and for sharing unpublished data, P. Morgan for sharing unpublished data, J. Pierce-Shimomura for sharing unc-80 mapping data, M. Alion for unc-80(ox330) and unc-80(ox329), G. Hollopeter for the Punc-17:mCherry strain, M. Gu for the GFP-tagged synaptotagmin strain, B. Grant, K. Sato, and M. Gu for the GFP-tagged clathrin strain, the C. elegans Genome Center for strains, and W. Davis for critical reading of the manuscript. Additionally, we would like to thank J. Weis, N. Jorgensen, and D. Lewis for technical assistance. The research was funded by grants from the National Institutes of Health (NS48391 to K.S., NS034307 to E.M.J) and from the Lowe Syndrome Association and the Lowe Syndrome Trust to K.S. and E.M.J. E.M.J. is an Investigator of the Howard Hughes Medical Institute, T.P.S. is supported by an operating grant from the Canadian Institutes for Health Research and a Canada Research Chair, and M.J. is supported by a long-term fellowship from Human Frontier Science Program.

PY - 2007/9/18

Y1 - 2007/9/18

N2 - Synaptojanin 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.

AB - Synaptojanin 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.

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KW - MOLNEURO

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U2 - 10.1016/j.cub.2007.08.036

DO - 10.1016/j.cub.2007.08.036

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AN - SCOPUS:34548499323

SN - 0960-9822

VL - 17

SP - 1595

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JO - Current Biology

JF - Current Biology

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ER -

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

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Keywords

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