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

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Title: Recycling of the human prostacyclin receptor is regulated through a direct interaction with Rab11a GTPase
Authors: Wikström, Katarina
Reid, Helen M.
Hill, Maria
English, Karol A.
O'Keeffe, Martina B.
Kimbembe, Cisca C.
Kinsella, B. Therese
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Date: Dec-2008
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.
Funding Details: Science Foundation Ireland
Type of material: Journal Article
Publisher: Elsevier
Journal: Cellular Signalling
Volume: 20
Issue: 12
Start page: 2332
End page: 2346
Copyright (published version): 2008 Elsevier Inc.
Keywords: Human prostacyclin receptorInternalizationRab11aRab4aYeast-two-hybridGPCR
Subject LCSH: Prostacyclin
Protein-protein interactions
G proteins
DOI: 10.1016/j.cellsig.2008.09.003
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Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
Biomolecular and Biomedical Science Research Collection

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