RRC ID 46385
Author Kimata T, Tanizawa Y, Can Y, Ikeda S, Kuhara A, Mori I.
Title Synaptic polarity depends on phosphatidylinositol signaling regulated by myo-inositol monophosphatase in Caenorhabditis elegans.
Journal Genetics
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.
Volume 191(2)
Pages 509-21
Published 2012-6-1
DOI 10.1534/genetics.111.137844
PII genetics.111.137844
PMID 22446320
PMC PMC3374314
MeSH 5'-Nucleotidase / genetics 5'-Nucleotidase / metabolism* Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Lithium Chloride / pharmacology Mutation Nerve Tissue Proteins / metabolism Phosphatidylinositols / metabolism* Phospholipase C beta / genetics Phosphoric Monoester Hydrolases / genetics Phosphoric Monoester Hydrolases / metabolism* Protein Transport Signal Transduction* Synapses / drug effects Synapses / metabolism*
IF 4.015
Times Cited 13
C.elegans tm1447 tm2348 tm3741 tm753