GPCR-induced calcium transients trigger nuclear actin assembly for chromatin dynamics

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Cytoplasmic actin cytoskeleton is well-studied, but nuclear actin filament regulation and function are emerging fields.
• Previous work showed serum-induced nuclear actin assembly, but triggers and mechanisms were unknown.

Purpose of the Study:

• To elucidate the extracellular cues, receptors, and signaling pathways that regulate nuclear F-actin assembly.
• To investigate the role of nuclear actin in chromatin organization and cellular responses.

Main Methods:

• Utilized physiological ligands for G protein-coupled receptors (GPCRs).
• Investigated signaling pathways involving heterotrimeric Gαq proteins and calcium release from the endoplasmic reticulum (ER).
• Examined the role of the ER-associated formin INF2 at the inner nuclear membrane (INM) and its targeting by calcium.

Main Results:

• GPCR activation by physiological ligands promotes nuclear F-actin assembly via Gαq proteins.
• Nuclear actin assembly requires calcium release from the ER, targeting INF2 at the INM.
• Calcium signaling induces polymerization of linear actin filaments from the INM into the nucleus.
• GPCRs and elevated calcium trigger nuclear actin-dependent alterations in chromatin organization.

Conclusions:

• A novel mechanism is uncovered where physiological ligands and calcium promote nuclear F-actin assembly.
• This pathway mediates rapid cellular responses by influencing chromatin dynamics.
• Nuclear actin plays a crucial role in regulating chromatin organization in response to extracellular signals.