| First Author | Scherer SL | Year | 2017 |
| Journal | J Biol Chem | Volume | 292 |
| Issue | 24 | Pages | 9906-9918 |
| PubMed ID | 28432124 | Mgi Jnum | J:245990 |
| Mgi Id | MGI:5917712 | Doi | 10.1074/jbc.M116.771923 |
| Citation | Scherer SL, et al. (2017) Regulation of neurite morphogenesis by interaction between R7 regulator of G protein signaling complexes and G protein subunit Galpha13. J Biol Chem 292(24):9906-9918 |
| abstractText | The R7 regulator of G protein signaling family (R7-RGS) critically regulates nervous system development and function. Mice lacking all R7-RGS subtypes exhibit diverse neurological phenotypes, and humans bearing mutations in the retinal R7-RGS isoform RGS9-1 have vision deficits. Although each R7-RGS subtype forms heterotrimeric complexes with Gbeta5 and R7-RGS-binding protein (R7BP) that regulate G protein-coupled receptor signaling by accelerating deactivation of Gi/o alpha-subunits, several neurological phenotypes of R7-RGS knock-out mice are not readily explained by dysregulated Gi/o signaling. Accordingly, we used tandem affinity purification and LC-MS/MS to search for novel proteins that interact with R7-RGS heterotrimers in the mouse brain. Among several proteins detected, we focused on Galpha13 because it had not been linked to R7-RGS complexes before. Split-luciferase complementation assays indicated that Galpha13 in its active or inactive state interacts with R7-RGS heterotrimers containing any R7-RGS isoform. LARG (leukemia-associated Rho guanine nucleotide exchange factor (GEF)), PDZ-RhoGEF, and p115RhoGEF augmented interaction between activated Galpha13 and R7-RGS heterotrimers, indicating that these effector RhoGEFs can engage Galpha13.R7-RGS complexes. Because Galpha13/R7-RGS interaction required R7BP, we analyzed phenotypes of neuronal cell lines expressing RGS7 and Gbeta5 with or without R7BP. We found that neurite retraction evoked by Galpha12/13-dependent lysophosphatidic acid receptors was augmented in R7BP-expressing cells. R7BP expression blunted neurite formation evoked by serum starvation by signaling mechanisms involving Galpha12/13 but not Galphai/o These findings provide the first evidence that R7-RGS heterotrimers interact with Galpha13 to augment signaling pathways that regulate neurite morphogenesis. This mechanism expands the diversity of functions whereby R7-RGS complexes regulate critical aspects of nervous system development and function. |
