The P-type ATPase CATP-1 is a novel regulator ofC. elegansdevelopmental timing that acts independently of its predicted pump function

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.

Identification of a Novel Transport-independent Function of PiT1/SLC20A1 in the Regulation of TNF-induced Apoptosis

“…They are involved in morphogenesis and oncogenesis, and these functions are independent of their transport activity (49 -51). In Caenorhabditis elegans, the cation-transporting ATPase CATP-1 interacts with the insulin/IGF and Ras-MAPK pathways to control several postembryonic events, independently of its transport function (52). A potential extracellular ligand has not been identified in this case.…”

Na+/K+ ATPase regulates the expression and localization of acetylcholine receptors in a pump activity-independent manner

“…The C. elegans genome encodes five Na + /K + ATPase α subunits, EAT-6, C01G12.8, C09H5.2, C02E7.1 and CATP-1 (Okamura et al, 2003;Ruaud and Bessereau, 2007). catp-1 is expressed in the epidermal cells and the excretory duct cell (Ruaud and Bessereau, 2007). Using GFP fusion constructs, we found that C01G12.8 was expressed in the germline, C09H5.2 in hypodermal cells, and C02E7.1 undetected in any tissues.…”

“…To clarify the tissue-specific expression profile of eat-6, we also examined the expression patterns of other Na + /K + ATPase α subunits in the C. elegans genome. The C. elegans genome encodes five Na + /K + ATPase α subunits, EAT-6, C01G12.8, C09H5.2, C02E7.1 and CATP-1 (Okamura et al, 2003;Ruaud and Bessereau, 2007). catp-1 is expressed in the epidermal cells and the excretory duct cell (Ruaud and Bessereau, 2007).…”

“…In C. elegans, another P-type ATPase CATP-1, which is distantly related to EAT-6 and vertebrate Na + /K + ATPase, regulates larval developmental timing through the insulin/IGF and Ras-MAPK pathways (Ruaud and Bessereau, 2007). Pump activity is not required for this regulation because pump-dead CATP-1 rescues the developmental delay in catp-1 mutants.…”

Mos1-mediated insertional mutagenesis in Caenorhabditis elegans

“…15) in the germ line of C. elegans 16,17 .This technique has been used successfully in forward genetic screens to identify genes of interest [18][19][20][21] . This system has three main advantages.…”