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Published on: November 11, 2018
Activated Galphaq family members induce Rho GTPase activation and Rho-dependent actin filament assembly
Parmesh Dutt1, Lars Kjoller, Maryann Giel
1Physiology Department, 136 Harrison Avenue, Tufts University School of Medicine, Boston, MA 02111, USA.
Abstract:
Rho GTPase is required for actin filament assembly and serum response element (SRE)-dependent gene transcription. Certain G protein-coupled receptors (GPCRs) induce Rho-dependent responses, but the intermediary signaling steps are poorly understood. The heterotrimeric Galpha12 family can induce Rho-dependent responses. In contrast, there are conflicting reports on the role of the Galphaq family in Rho signaling. We report that expression of activated Galphaq members, or activation of endogenous Galphaq via GPCR stimulation, induces SRE reporter activation via Rho, and increased GTP-Rho levels. Moreover, microinjection of activated Galphaq in fibroblasts induces actin stress fiber formation via Rho. Galphaq functionally cooperates with Lbc Rho guanine nucleotide exchange factor. Overall, these findings indicate that Galphaq family signals are sufficient to induce Rho-dependent cellular responses.
Insights
The Galphaq protein family activates Rho GTPase signaling, which is crucial for gene transcription and actin assembly. This study clarifies Galphaq
Area of Science:
- Cellular signaling pathways
- Molecular biology
- G protein-coupled receptor (GPCR) research
Background:
- Rho GTPase is essential for actin filament assembly and serum response element (SRE)-dependent gene transcription.
- The signaling pathways linking G protein-coupled receptors (GPCRs) to Rho activation are not fully understood.
- While the Galpha12 family is known to induce Rho-dependent responses, the role of the Galphaq family remains controversial.
Purpose of the Study:
- To investigate the role of the Galphaq protein family in Rho signaling pathways.
- To determine if Galphaq activation is sufficient to induce Rho-dependent cellular responses.
Main Methods:
- Expression of activated Galphaq members and activation of endogenous Galphaq via GPCR stimulation.
- Measurement of SRE reporter activation and GTP-Rho levels.
- Microinjection of activated Galphaq into fibroblasts to observe actin stress fiber formation.
- Assessment of functional cooperation with Lbc Rho guanine nucleotide exchange factor.
Main Results:
- Activation of Galphaq, either by expression or GPCR stimulation, leads to SRE reporter activation and increased GTP-Rho levels.
- Microinjection of activated Galphaq induces Rho-dependent actin stress fiber formation in fibroblasts.
- Galphaq functionally cooperates with the Lbc Rho guanine nucleotide exchange factor.
Conclusions:
- Galphaq family signaling is sufficient to induce Rho-dependent cellular responses, including gene transcription and actin organization.
- This study clarifies the role of Galphaq in Rho signaling, resolving conflicting previous reports.
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