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Synaptic polarity depends on phosphatidylinositol signaling regulated by myo-inositol monophosphatase in Caenorhabditis elegans.

Tsubasa Kimata | Yoshinori Tanizawa | Yoko Can | Shingo Ikeda | Atsushi Kuhara | Ikue Mori
Genetics | 2012

Although neurons are highly polarized, how neuronal polarity is generated remains poorly understood. An evolutionarily conserved inositol-producing enzyme myo-inositol monophosphatase (IMPase) is essential for polarized localization of synaptic molecules in Caenorhabditis elegans and can be inhibited by lithium, a drug for bipolar disorder. The synaptic defect of IMPase mutants causes defects in sensory behaviors including thermotaxis. Here we show that the abnormalities of IMPase mutants can be suppressed by mutations in two enzymes, phospholipase Cβ or synaptojanin, which presumably reduce the level of membrane phosphatidylinositol 4,5-bisphosphate (PIP(2)). We also found that mutations in phospholipase Cβ conferred resistance to lithium treatment. Our results suggest that reduction of PIP(2) on plasma membrane is a major cause of abnormal synaptic polarity in IMPase mutants and provide the first in vivo evidence that lithium impairs neuronal PIP(2) synthesis through inhibition of IMPase. We propose that the PIP(2) signaling regulated by IMPase plays a novel and fundamental role in the synaptic polarity.

Pubmed ID: 22446320

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WormBase (tool)

RRID:SCR_003098

Central data repository for nematode biology including complete genomic sequence, gene predictions and orthology assignments from range of related nematodes.Data concerning genetics, genomics and biology of C. elegans and related nematodes. Derived from initial ACeDB database of C. elegans genetic and sequence information, WormBase includes genomic, anatomical and functional information of C. elegans, other Caenorhabditis species and other nematodes. Maintains public FTP site where researchers can find many commonly requested files and datasets, WormBase software and prepackaged databases.

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Wako (tool)

RRID:SCR_013651

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Center for Iron and Heme Disorders at the University of Utah Mutation Generation and Detection Core (tool)

RRID:SCR_015339

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VC2053 (tool)

RRID:WB-STRAIN:WBStrain00037056

Caenorhabditis elegans with name wip-1(ok2435) III/hT2 [bli-4(e937) let-?(q782) qIs48] (I;III). from WB.

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IK575 (tool)

RRID:WB-STRAIN:WBStrain00021999

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VC728 (tool)

RRID:WB-STRAIN:WBStrain00036017

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VC381 (tool)

RRID:WB-STRAIN:WBStrain00035722

Caenorhabditis elegans with name atm-1(gk186) I. from WB.

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