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Lamina-associated polypeptide 2α is required for intranuclear MRTF-A activity.

Ekaterina Sidorenko1, Maria Sokolova1, Antti P Pennanen1

  • 1Institute of Biotechnology, University of Helsinki, Helsinki, Finland.

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|February 11, 2022
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Lamina-associated polypeptide 2α (Lap2α) is a novel nuclear regulator of Myocardin-related transcription factor A (MRTF-A). Lap2α is essential for MRTF-A/SRF target gene expression and serum-induced cell migration.

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Transcriptional Regulation

Background:

  • Myocardin-related transcription factor A (MRTF-A) is a key coactivator of serum response factor (SRF).
  • MRTF-A regulates cytoskeletal gene expression in response to actin dynamics.
  • Existing regulators of MRTF-A primarily act by controlling its nuclear localization.

Purpose of the Study:

  • To identify novel mechanisms regulating MRTF-A activity within the nucleus.
  • To investigate the role of lamina-associated polypeptide 2α (Lap2α) in MRTF-A-mediated transcription.
  • To elucidate the functional consequences of Lap2α-MRTF-A interaction.

Main Methods:

  • Co-immunoprecipitation assays to confirm MRTF-A and Lap2α binding.
  • Quantitative PCR and Western blotting to assess gene expression.
  • Cell migration assays to evaluate phenotypic effects.
  • Chromatin immunoprecipitation to analyze histone modifications.

Main Results:

  • Lap2α directly binds to MRTF-A within the nucleus.
  • Lap2α is required for efficient recruitment of MRTF-A to its target genes, independent of nuclear localization.
  • Lap2α's function precedes MRTF-A chromatin binding and does not directly affect histone marks.
  • Loss of Lap2α impairs serum-induced cell migration and may influence muscle and proliferation phenotypes.

Conclusions:

  • Lap2α represents a novel nuclear regulator of MRTF-A activity.
  • Lap2α facilitates MRTF-A/SRF target gene expression by promoting MRTF-A recruitment, not localization.
  • This study expands the known functions of Lap2α in transcriptional regulation and highlights a new layer of control for MRTF-A-SRF signaling.