Nuclear actin network assembly by formins regulates the SRF coactivator MAL.

Abstract

Formins are potent activators of actin filament assembly in the cytoplasm. In turn, cytoplasmic actin polymerization can promote release of actin from megakaryocytic acute leukemia (MAL) protein for serum response factor (SRF) transcriptional activity. We found that formins polymerized actin inside the mammalian nucleus to drive serum-dependent MAL-SRF activity. Serum stimulated rapid assembly of actin filaments within the nucleus in a formin-dependent manner. The endogenous formin mDia was regulated with an optogenetic tool, which allowed for photoreactive release of nuclear formin autoinhibition. Activated mDia promoted rapid and reversible nuclear actin network assembly, subsequent MAL nuclear accumulation, and SRF activity. Thus, a dynamic polymeric actin structure within the nucleus is part of the serum response.

• Authors: Christian Baarlink, Haicui Wang, Robert Grosse
• Journal: Science (New York, N.Y.) (Science) Vol. 340 Issue 6134 Pg. 864-7 (May 17 2013) ISSN: 1095-9203 [Electronic] United States
• PMID: 23558171 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Carrier Proteins
• Diap1 protein, mouse
• Formins
• Intracellular Signaling Peptides and Proteins
• Microtubule-Associated Proteins
• Nuclear Localization Signals
• Serum Response Factor
• megakaryocytic acute leukemia protein, mouse
• Dia2 protein, mouse
• NADPH Dehydrogenase

Topics

• Actins (metabolism)
• Animals
• Carrier Proteins (metabolism)
• Cell Nucleus (metabolism)
• Formins
• HeLa Cells
• Humans
• Intracellular Signaling Peptides and Proteins (metabolism)
• Metabolic Networks and Pathways
• Mice
• Microtubule-Associated Proteins (metabolism)
• NADPH Dehydrogenase (metabolism)
• NIH 3T3 Cells
• Nuclear Localization Signals (metabolism)
• Polymerization
• Serum (metabolism)
• Serum Response Factor (agonists)