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PMID:22446320

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Citation

Kimata, T, Tanizawa, Y, Can, Y, Ikeda, S, Kuhara, A and Mori, I (2012) Synaptic polarity depends on phosphatidylinositol signaling regulated by myo-inositol monophosphatase in Caenorhabditis elegans. Genetics 191:509-21

Abstract

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.

Links

PubMed PMC3374314 Online version:10.1534/genetics.111.137844

Keywords


Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CAEEL:PLCB

involved_in

GO:0006935: chemotaxis

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00008765

P

Seeded From UniProt

complete

CAEEL:PLCB

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:PLCB

involved_in

GO:0043052: thermotaxis

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00008765

P

Seeded From UniProt

complete

CAEEL:PLCB

involved_in

GO:0035418: protein localization to synapse

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00008765

P

Seeded From UniProt

complete

CAEEL:SYNJ

involved_in

GO:0035418: protein localization to synapse

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00008765

P

Seeded From UniProt

complete

CAEEL:IMPA1

involved_in

GO:0006935: chemotaxis

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00091284

P

Seeded From UniProt

complete

CAEEL:IMPA1

involved_in

GO:0043052: thermotaxis

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00091282
WB:WBVar00091284

P

Seeded From UniProt

complete

CAEEL:IMPA1

involved_in

GO:0035418: protein localization to synapse

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00091284

P

Seeded From UniProt

complete


See also

References

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