RDJ2 (DNAJA2) chaperones neural G protein signaling pathways
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A number of structurally divergent proteins with J domains, called J proteins, interact with and activate the ATPase of Hsp70s, thereby harnessing the ATPase activity for conformational work on target proteins. The precise role of most mammalian J proteins remains undefined. In this paper, we demonstrate that transient expression of the J protein, Rdj2, in HEK 293 cells increased cellular cyclic adenosine monophosphate (cAMP) levels in the presence of the β-adrenergic agonist isoproterenol. In CNS-derived catecholaminergic neuronal cell line (CAD) neuroblastoma cells, expression of Rdj2 increased isoproterenol-stimulated phosphorylation of cAMP response element binding protein (CREB). Moreover, we have characterized the binding properties of Rdj2 and observed a direct interaction between Rdj2 and receptor-coupled trimeric GTP-binding proteins (G proteins). We further show that the composition of the Rdj2-chaperone complex and the cysteine string protein (CSPα)-chaperone complex, another J protein, is distinct. Our data demonstrate that Rdj2 modulates G protein signaling and further suggest that chaperoning G proteins is an emerging theme of the J protein network.
KeywordsRdj2 J protein CSPα Cysteine string protein G protein
This work was supported by funding from the Alberta Prion Research Institute and the Canadian Institute of Health Research. We are grateful to Dr. L. Greene (National Institute of Health) for anti-auxilin polyclonal, to Dr. E. Lafer (University of Texas) for GST-auxilin construct, to Dr. M. Nyugen (University of Calgary) for CAD neuroblastoma cells, and Dr. M Bouvier (Université de Montréal) for the pcDNA3 β2 adrenergic receptor construct. APB is an Alberta Heritage Foundation for Medical Research Senior Scholar. JEAB is an Alberta Heritage Foundation for Medical Research Senior Scholar.
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