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RhoA controls retinoid signaling by ROCK dependent regulation of retinol metabolism

Alberto García-Mariscal1, Karine Peyrollier1, Astrid Basse1

  • 1a Department of Biomedical Sciences , BRIC, University of Copenhagen , Copenhagen , Denmark.

Small Gtpases
|October 19, 2016
PubMed

Insights

The small GTPase RhoA, crucial for development and cancer, unexpectedly regulates gene expression via retinoid signaling. Loss of RhoA impairs retinoic acid receptor activity and alters target gene expression in mouse keratinocytes.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • RhoA is a small GTPase vital for embryonic development and implicated in cancer.
  • RhoA is primarily known for regulating the actin cytoskeleton.
  • Its role in gene regulation remains less understood.

Purpose of the Study:

  • To investigate the impact of RhoA loss on gene expression in primary mouse keratinocytes.
  • To explore the connection between RhoA and retinoid signaling pathways.

Main Methods:

  • Utilized primary mouse keratinocytes with RhoA gene deletion.
  • Performed transcription factor reporter assays (RAR luciferase reporter).
  • Assessed the effect of RhoA effector ROCK inhibition and retinoids (ATRA, retinal, retinol).

Main Results:

  • RhoA-null keratinocytes showed significantly decreased RAR luciferase reporter activity.
  • Inhibition of ROCK mimicked the RhoA-null phenotype.
  • All-trans retinoic acid (ATRA) and retinal, but not retinol, restored RAR reporter activity in RhoA/ROCK-impaired cells.
  • A notable percentage of known ATRA target genes exhibited altered expression in RhoA-null keratinocytes.

Conclusions:

  • RhoA signaling is unexpectedly linked to retinoid signaling.
  • RhoA regulates gene expression through a novel pathway involving retinoid metabolism.
  • This discovery provides new insights into RhoA's function beyond cytoskeletal regulation.
Keywords:
ROCKRhoAretinoic acidskinstem cells

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