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PMID:17251264

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Citation

Ruaud, AF and Bessereau, JL (2007) The P-type ATPase CATP-1 is a novel regulator of C. elegans developmental timing that acts independently of its predicted pump function. Development 134:867-79

Abstract

During postembryonic stages, metazoans synchronize the development of a large number of cells, tissues and organs by mechanisms that remain largely unknown. In Caenorhabditis elegans larvae, an invariant cell lineage is tightly coordinated with four successive molts, thus defining a genetically tractable system to analyze the mechanisms underlying developmental synchronization. Illegitimate activation of nicotinic acetylcholine receptors (nAChRs) by the nicotinic agonist dimethylphenylpiperazinium (DMPP) during the second larval stage (L2) of C. elegans causes a lethal heterochronic phenotype. DMPP exposure delays cell division and differentiation without affecting the molt cycle, hence resulting in deadly exposure of a defective cuticle to the surrounding environment. In a screen for DMPP-resistant mutants, we identified catp-1 as a gene coding for a predicted cation-transporting P-type ATPase expressed in the epidermis. Larval development was specifically slowed down at the L2 stage in catp-1 mutants compared with wild-type animals and was not further delayed after exposure to DMPP. We demonstrate that CATP-1 interacts with the insulin/IGF and Ras-MAPK pathways to control several postembryonic developmental events. Interestingly, these developmental functions can be fulfilled independently of the predicted cation-transporter activity of CATP-1, as pump-dead engineered variants of CATP-1 can rescue most catp-1-mutant defects. These results obtained in vivo provide further evidence for the recently proposed pump-independent scaffolding functions of P-type ATPases in the modulation of intracellular signaling.

Links

PubMed Online version:10.1242/dev.02790

Keywords

Amino Acid Sequence; Animals; Caenorhabditis elegans/growth & development; Caenorhabditis elegans/metabolism; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/physiology; Cell Differentiation; Cell Division; Cell Lineage; Dimethylphenylpiperazinium Iodide/pharmacology; Insulin/metabolism; Larva; MAP Kinase Signaling System/physiology; Molecular Sequence Data; Molting; Mutation; Nicotinic Agonists/pharmacology; Phylogeny; Proton-Translocating ATPases/genetics; Proton-Translocating ATPases/physiology; Receptor, Insulin/metabolism; Signal Transduction

Significance

Annotations

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

CAEEL:G5EBE7

involved_in

GO:0002119: nematode larval development

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00088267

P

Seeded From UniProt

complete

CAEEL:G5EBE7

involved_in

GO:0040024: dauer larval development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00000898

P

Seeded From UniProt

complete

CAEEL:G5EC38

involved_in

GO:0002119: nematode larval development

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00088267

P

Seeded From UniProt

complete

CAEEL:G5EC38

involved_in

GO:0040024: dauer larval development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00000898

P

Seeded From UniProt

complete


See also

References

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