G Protein GalphaQ Subunits Engage Targets in the Nucleus Involved in Chromatin Remodeling and RNA Splicing

ABSTRACT: G𝛼q is a critical mediator of cell and tissue responses to stimulation of Gq-coupled receptors that regulate PLCbeta and RhoGEFs. To identify novel G𝛼q signaling partners, we performed a proximity labeling proteomic screen in HEK293A cells using TurboID-tagged GalphaQ. Top GalphaQ(Q209L) enriched proteins included known G𝛼q interactors (PLCbetas, RhoGEFs, and GRK2), supporting the validity of this approach. Also highly enriched were several nuclear proteins including SMARCD3 (BAF60c), a component of the SWI/SNF chromatin remodeling complex, and BCAS2 a component of the spliceosome, both of which are nuclear proteins. Luciferase complementation experiments show that GalphaQ selectively interacts with BCAS2 and SMARCD3 in an activation-dependent manner, and pulldown experiments with purified components demonstrate direct interaction of GalphaQ and SMARCD3. We also show that a small but significant portion of GalphaQ is present in the nucleus, and this is increased following GPCR activation or or introduction of an activating mutation. Proximity ligation assays indicate that GalphaQ(Q209L) engages SMARCD3 in the nucleus. These data suggest that GalphaQ engages downstream targets in the nucleus and could therefore directly regulate nuclear processes

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Alan Smrcka  

LAB HEAD: Alan V Smrcka

PROVIDER: PXD071839 | Pride | 2026-05-25

REPOSITORIES: Pride