title: Vps26B-retromer negatively regulates plasma membrane resensitization of PAR-2.
abstract: Retromer is a trimeric complex composed of Vps26, Vps29, and Vps35 and has been shown to be involved in trafficking and sorting of transmembrane proteins within the endosome. The Vps26 paralog, Vps26B, defines a distinct retromer complex (Vps26B-retromer) in vivo and in vitro. Although endosomally associated, Vps26B-retromer does not bind the established retromer transmembrane cargo protein, cation-independent mannose 6-phosphate receptor (CI-M6PR), indicating it has a distinct role to retromer containing the Vps26A paralog. In the present study we use the previously established Vps26B-expressing HEK293 cell model to address the role of Vps26B-retromer in trafficking of the protease activated G-protein coupled receptor PAR-2 to the plasma membrane. In these cells there is no apparent defect in the initial activation of the receptor, as evidenced by release of intracellular calcium, ERK1/2 signaling and endocytosis of activated receptor PAR-2 into degradative organelles. However, we observe a significant delay in plasma membrane repopulation of the protease activated G protein-coupled receptor PAR-2 following stimulation, resulting in a defect in PAR-2 activation after resensitization. Here we propose that PAR-2 plasma membrane repopulation is regulated by Vps26B-retromer, describing a potential novel role for this complex.
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane 4072, Australia.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bugarcic
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane 4072, Australia.
authors.forename: Irina
authors.initials: I
authors.lastname: Vetter
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane 4072, Australia.
authors.forename: Silke
authors.initials: S
authors.lastname: Chalmers
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane 4072, Australia.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Kinna
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane 4072, Australia.
authors.forename: Brett M
authors.initials: BM
authors.lastname: Collins
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane 4072, Australia.
authors.forename: Rohan D
authors.initials: RD
authors.lastname: Teasdale
mesh_terms: D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D011992:Endosomes / Q000378:metabolism; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D052139:Intracellular Calcium-Sensing Proteins / Q000378:metabolism; D021381:Protein Transport; D044464:Receptor, PAR-2 / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D052139:Intracellular Calcium-Sensing Proteins; D044464:Receptor, PAR-2; C498296:VPS26A protein, human; D033921:Vesicular Transport Proteins; D002118:Calcium
keywords: PAR-2; Vps26B; endosome; protein trafficking; retromer