Recycling of the human prostacyclin receptor is regulated through a direct interaction with Rab11a GTPase

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Show simple item record Wikström, Katarina Reid, Helen M. Hill, Maria English, Karol A. O'Keeffe, Martina B. Kimbembe, Cisca C. Kinsella, B. Therese 2011-09-01T14:31:42Z 2011-09-01T14:31:42Z 2008 Elsevier Inc. en 2008-12
dc.identifier.citation Cellular Signalling en
dc.identifier.issn 0898-6568
dc.description.abstract The human prostacyclin receptor (hIP) undergoes agonist-induced internalization but the mechanisms regulating its intracellular trafficking and/or recycling to the plasma membrane are poorly understood. Herein, we conducted a yeast-two-hybrid screen to identify proteins interacting with the carboxyl terminal (C)-tail domain of the hIP and discovered a novel interaction with Rab11a. This interaction was confirmed by co-immunoprecipitations in mammalian HEK293 and was augmented by cicaprost stimulation. The hIP co-localized to Rab11-containing recycling endosomes in both HEK293 and endothelial EA.hy 926 cells in a time dependent manner following cicaprost stimulation. Moreover, over-expression of Rab11a significantly increased recycling of the hIP, while the dominant negative Rab11S25N impaired that recycling. Conversely, while the hIP co-localized to Rab4-positive endosomes in response to cicaprost, ectopic expression of Rab4a did not substantially affect overall recycling nor did Rab4a directly interact with the hIP. The specific interaction between the hIP and Rab11a was dependent on a 22 amino acid (Val299 – Gln320) sequence within its C-tail domain and was independent of isoprenylation of the hIP. This study elucidates a critical role for Rab11a in regulating trafficking of the hIP and has identified a novel Rab11 binding-domain (RBD) within its C-tail domain that is both necessary and sufficient to mediate interaction with Rab11a. en
dc.description.sponsorship Science Foundation Ireland en
dc.format.extent 1652615 bytes
dc.format.mimetype application/pdf
dc.language.iso en en
dc.publisher Elsevier en
dc.relation.requires Biomolecular and Biomedical Science Research Collection en
dc.relation.requires Conway Institute Research Collection en
dc.rights This is the author’s version of a work that was accepted for publication in Cellular Signalling. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Cellular Signalling (2008), 20(12):2332-46 DOI 10.1016/j.cellsig.2008.09.003. en
dc.subject Human prostacyclin receptor en
dc.subject Internalization en
dc.subject Rab11a en
dc.subject Rab4a en
dc.subject Yeast-two-hybrid en
dc.subject GPCR en
dc.subject.lcsh Prostacyclin en
dc.subject.lcsh Protein-protein interactions en
dc.subject.lcsh G proteins en
dc.subject.mesh Receptors, Prostaglandin en
dc.subject.mesh rab GTP-Binding Proteins en
dc.subject.mesh Two-Hybrid System Techniques en
dc.subject.mesh Receptors, G-Protein-Coupled en
dc.title Recycling of the human prostacyclin receptor is regulated through a direct interaction with Rab11a GTPase en
dc.type Journal Article en
dc.internal.availability Full text available en
dc.internal.webversions en
dc.status Peer reviewed en
dc.identifier.volume 20 en
dc.identifier.issue 12 en
dc.identifier.startpage 2332 en
dc.identifier.endpage 2346 en
dc.identifier.doi 10.1016/j.cellsig.2008.09.003
dc.neeo.contributor Wikström|Katarina|aut| en
dc.neeo.contributor Reid|Helen M.|aut| en
dc.neeo.contributor Hill|Maria|aut| en
dc.neeo.contributor English|Karol A.|aut| en
dc.neeo.contributor O'Keeffe|Martina B.|aut| en
dc.neeo.contributor Kimbembe|Cisca C.|aut| en
dc.neeo.contributor Kinsella|B. Therese|aut| en
dc.description.othersponsorship Wellcome Trust en
dc.description.admin ti, ab, ke,-SB 01/09/2011 en

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