PhLP1 acts as a general mediator of Gβγ and Gβ 5 RGS protein dimer assembly

Phosducin‐like protein 1 (PhLP1) has been recently shown to be an essential chaperone in the folding and assembly of nascent G protein βγ subunit dimer (Gβγ). However, the role of PhLP1 has only been tested for the most common Gβγ combination Gβ 1 γ 2 , yet there are 5 Gβ subunits and 12 Gγ subunits that form dimers in various combinations. In addition, Gβ 5 forms important dimers with the R7 family of regulators of G protein signaling (RGS). The current study was designed to answer three questions with regard to the generality of the chaperone role of PhLP1: 1) Does PhLP1 catalyze the assembly of all Gβγ combinations or just a subset? 2) Does PhLP1 influence the specificity of Gβγ dimer formation? and 3) Does PhLP1 contribute to the assembly of Gβ 5 RGS complexes? Our data show that PhLP1 is necessary for the assembly of all five Gβ subunits with Gγ 2 and of all Gγ subunits that form dimers with Gβ 2 . Moreover, PhLP1 did not change the preference of Gβ 2 for certain Gγs. Finally, PhLP1 was required for Gβ 5 ‐RGS9 assembly, but less so for Gβ 5 ‐RGS7 assembly. These results show that PhLP1 is a general chaperone for dimer formation of all Gβγ combinations and for at least a subset of Gβ 5 ‐RGS complexes.