| RRC ID |
46385
|
| 著者 |
Kimata T, Tanizawa Y, Can Y, Ikeda S, Kuhara A, Mori I.
|
| タイトル |
Synaptic polarity depends on phosphatidylinositol signaling regulated by myo-inositol monophosphatase in Caenorhabditis elegans.
|
| ジャーナル |
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.
|
| 巻・号 |
191(2)
|
| ページ |
509-21
|
| 公開日 |
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
|
| 引用数 |
13
|
|
WOS 分野
|
GENETICS & HEREDITY
|
| リソース情報 |
| 線虫 |
tm1447
tm2348
tm3741
tm753 |
