| First Author | Akturk A | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 42 | Pages | eabq2826 |
| PubMed ID | 36260679 | Mgi Jnum | J:330604 |
| Mgi Id | MGI:7379710 | Doi | 10.1126/sciadv.abq2826 |
| Citation | Akturk A, et al. (2022) RGS12 polarizes the GPSM2-GNAI complex to organize and elongate stereocilia in sensory hair cells. Sci Adv 8(42):eabq2826 |
| abstractText | Inhibitory G proteins (GNAI/Galpha<sub>i</sub>) bind to the scaffold G protein signaling modulator 2 (GPSM2) to form a conserved polarity complex that regulates cytoskeleton organization. GPSM2 keeps GNAI in a guanosine diphosphate (GDP)-bound state, but how GPSM2-GNAI is generated or relates to heterotrimeric G protein signaling remains unclear. We find that RGS12, a GTPase-activating protein (GAP), is required to polarize GPSM2-GNAI at the hair cell apical membrane and to organize mechanosensory stereocilia in rows of graded heights. Accordingly, RGS12 and the guanine nucleotide exchange factor (GEF) DAPLE are asymmetrically co-enriched at the hair cell apical junction, and <i>Rgs12</i> mouse mutants are deaf. GPSM2 and RGS12 share GoLoco motifs that stabilize GNAI(GDP), and GPSM2 outcompetes RGS12 to bind GNAI. Our results suggest that polarized GEF/GAP junctional activity might dissociate heterotrimeric G proteins, generating free GNAI(GDP) for GPSM2 at the adjacent apical membrane. GPSM2-GNAI(GDP), in turn, imparts asymmetry to the forming stereocilia to enable sensory function in hair cells. |
