| http://purl.uniprot.org/citations/16630545 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16630545 | http://www.w3.org/2000/01/rdf-schema#comment | "Liddle's syndrome (excessive absorption of sodium ions) and PHA-1 (pseudohypoaldosteronism type 1) with decreased sodium absorption are caused by the mutations in the amiloride-sensitive epithelial sodium channel ENaC. Rab proteins are small GTPases involved in vesicle transport, docking, and fusion. Earlier, we reported that Rab27a inhibits ENaC-mediated currents through protein-protein interaction in HT-29 cells. We hereby report that Rab27a-dependent inhibition is associated with the GTP/GDP status as constitutively active or GTPase-deficient mutant Q78L inhibits amiloride-sensitive currents whereas GDP-locked inactive mutant T23N showed no effect. In order to further explore the molecular mechanism of this regulation, we performed competitive assays with two Rab27a-binding proteins: synaptotagmin-like protein (SLP-5) and Munc13-4 (a putative priming factor for exocytosis). Both proteins eliminate negative modulation of Rab27a on ENaC function. The SLP-5 reversal of Rab27a effect was restricted to C-terminal C2A/C2B domains assigned for putative phospholipids-binding function while the Rab27a-binding SHD motif imparted higher inhibition. The ENaC-mediated currents remain unaffected by Rab27a though SLP-5 appears to strongly bind it. The immunoprecipitation experiments suggest that in the presence of excessive Munc13-4 and SLP-5 proteins, Rab27a interaction with ENaC is diminished. Munc13-4 and SLP-5 limit the Rab27a availability to ENaC, thus minimizing its effect on channel function. These observations decisively prove that Rab27a inhibits ENaC function through a complex mechanism that involves GTP/GDP status, and protein-protein interactions involving Munc13-4 and SLP-5 effector proteins."xsd:string |
| http://purl.uniprot.org/citations/16630545 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.bbrc.2006.03.160"xsd:string |
| http://purl.uniprot.org/citations/16630545 | http://purl.uniprot.org/core/author | "Fukuda M."xsd:string |
| http://purl.uniprot.org/citations/16630545 | http://purl.uniprot.org/core/author | "Horiuchi H."xsd:string |
| http://purl.uniprot.org/citations/16630545 | http://purl.uniprot.org/core/author | "Saxena S.K."xsd:string |
| http://purl.uniprot.org/citations/16630545 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
| http://purl.uniprot.org/citations/16630545 | http://purl.uniprot.org/core/name | "Biochem Biophys Res Commun"xsd:string |
| http://purl.uniprot.org/citations/16630545 | http://purl.uniprot.org/core/pages | "651-657"xsd:string |
| http://purl.uniprot.org/citations/16630545 | http://purl.uniprot.org/core/title | "Rab27a regulates epithelial sodium channel (ENaC) activity through synaptotagmin-like protein (SLP-5) and Munc13-4 effector mechanism."xsd:string |
| http://purl.uniprot.org/citations/16630545 | http://purl.uniprot.org/core/volume | "344"xsd:string |
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