The actin-MRTF-SRF transcriptional circuit controls tubulin acetylation via a-TAT1 gene expression

The role of formins in microtubules is not well understood. In this study, we have investigated the mechanism by which INF2, a formin mutated in degenerative renal and neurological hereditary disorders, controls microtubule acetylation. We found that silencing of INF2 in epithelial RPE-1 cells produ...

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Bibliographic Details
Published inThe Journal of cell biology Vol. 217; no. 3; p. 929
Main Authors Fernández-Barrera, Jaime, Bernabé-Rubio, Miguel, Casares-Arias, Javier, Rangel, Laura, Fernández-Martín, Laura, Correas, Isabel, Alonso, Miguel A
Format Journal Article
LanguageEnglish
Published New York Rockefeller University Press 01.03.2018
Subjects
Acetylation
Acetyltransferase
Actin
Cells
Cellular biology
Circuits
Gene expression
Lymphocytes
Lymphocytes T
Microtubules
Neurological diseases
Ribonucleic acid
RNA
Serum response factor
Transcription activation
Tubulin
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Summary:The role of formins in microtubules is not well understood. In this study, we have investigated the mechanism by which INF2, a formin mutated in degenerative renal and neurological hereditary disorders, controls microtubule acetylation. We found that silencing of INF2 in epithelial RPE-1 cells produced a dramatic drop in tubulin acetylation, increased the G-actin/F-actin ratio, and impaired myocardin-related transcription factor (MRTF)/serum response factor (SRF)-dependent transcription, which is known to be repressed by increased levels of G-actin. The effect on tubulin acetylation was caused by the almost complete absence of α-tubulin acetyltransferase 1 (α-TAT1) messenger RNA (mRNA). Activation of the MRTF-SRF transcriptional complex restored α-TAT1 mRNA levels and tubulin acetylation. Several functional MRTF-SRF-responsive elements were consistently identified in the α-TAT1 gene. The effect of INF2 silencing on microtubule acetylation was also observed in epithelial ECV304 cells, but not in Jurkat T cells. Therefore, the actin-MRTF-SRF circuit controls α-TAT1 transcription. INF2 regulates the circuit, and hence microtubule acetylation, in cell types
ISSN:0021-9525
1540-8140