Complex interplay between RAS GTPases and RASSF effectors regulates subcellular localization of YAP

Related Experiment Video

Updated: Jun 21, 2025

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
10:27

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

10.8K

Swati Singh1, Gabriela Bernal Astrain1, Ana Maria Hincapie2

  • 1Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, H3T 1J4, Canada.

EMBO Reports
|July 15, 2024
PubMed

Insights

This study maps interactions between BRAF, RASSF proteins, and small GTPases, revealing new effector functions and signaling pathways. The research uncovers novel roles for RASSF proteins in cellular processes like Hippo signaling and mitochondrial dynamics.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • RAS GTPases are key regulators of cellular functions, translating upstream signals into downstream responses.
  • Effectors typically bind GTP-bound GTPases via specific domains like RBD/RA, but their specificity across the large RAS superfamily is not well understood.

Purpose of the Study:

  • To systematically map interactions between BRAF, RASSF effectors, and various small GTPases (RAS, RHO, ARF).
  • To explore the specificity of these interactions and uncover novel biological functions.
  • To investigate the roles of RASSF proteins in cellular signaling and organelle dynamics.

Main Methods:

  • Systematic mapping of protein-protein interactions.
  • Biochemical assays to validate GTPase-effector complexes.
  • Cellular assays to assess signaling pathway activation and organelle distribution.

Main Results:

  • 39 validated GTPase-effector complexes were identified, showing plasticity in RASSF binding.
  • BRAF exhibited specific binding to classical H/K/NRAS GTPases.
  • RASSF5-RAS interactions activated Hippo signaling and YAP sequestration.
  • RASSF8 formed phase-separated condensates with RAS and RHO GTPases.
  • RASSF3 was identified as a potential effector of mitochondrial MIRO proteins, influencing organelle distribution.

Conclusions:

  • Systematic mapping of GTPase-effector interactions reveals complex binding patterns and novel biological functions.
  • RASSF proteins play diverse roles, including regulating signaling pathways and organelle dynamics.
  • This approach can uncover previously unknown cellular processes mediated by GTPase-effector networks.
Keywords:
Hippo PathwayMIRORAS GTPaseRASSFYAP

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