RDJ2 (DNAJA2) chaperones neural G protein signaling pathways

Abstract

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.

The DNAJA2 Substrate Release Mechanism Is Essential for Chaperone-mediated Folding

“…Furthermore, knockdown of DJA1 reduced the clearance of misfolded mutant cystic fibrosis transmembrane regulator from the cell surface, and DJA2 knockdown did not (41). In contrast, DJA2 has been identified as an enhancer of G-protein-coupled signaling by the ␤2-adrenergic receptor (42). Although functions of DJA2 and DJA1 independent of Hsc70 are possible, it is generally thought that their main roles are as co-chaperones of Hsc70.…”

From hatching to dispatching: the multiple cellular roles of the Hsp70 molecular chaperone machinery

“…Also both Hsp70 proteins and DnaJ proteins have been shown to directly interact with GPCRs modulating their processing, whilst CSP binds G protein subunits. Furthermore, another DnaJ protein, Rdj2 (DnaJA2), has recently been shown to interact with G proteins and can modulate G protein signalling (Rosales-Hernandez et al 2008).…”

Heat shock proteins: Cellular and molecular mechanisms in the central nervous system

“…To date, we have a very limited understanding of this subclass A DNAJ protein. Localization studies have indicated that DNAJA2/Rdj2 is a neuroprotein expressed in all cell types of the whole rodent brain (Rosales-Hernandez et al , 2009). Moreover, DNAJA2/Rdj2 has been reported to be part of the multimeric chaperone complex with HSPA, HSPH, HSPC, HSP-interacting protein (Hip) and HSP organizing protein (Hop) (Craig et al , 2006).…”

“…Moreover, DNAJA2/Rdj2 has been reported to be part of the multimeric chaperone complex with HSPA, HSPH, HSPC, HSP-interacting protein (Hip) and HSP organizing protein (Hop) (Craig et al , 2006). In addition, DNAJA2/Rdj2 has been shown to associate with Gα and Gβ, which suggests that it is involved in G-protein signaling (Rosales-Hernandez et al , 2009). Ongoing efforts are underway to identify the specific G-protein signaling pathways and other functions of DNAJA2/Rdj2.…”