K-Ras controls asymmetric cell divisions from the primary cilium

Rohan Chippalkatti1, Elisabeth Schaffner-Reckinger1, Anthoula Gaigneaux2

  • 1Cancer Cell Biology and Drug Discovery group, Department of Health, Medicine and Life Sciences, University of Luxembourg, Esch-sur-Alzette, Luxembourg.

Cell Death & Disease
|July 11, 2026
PubMed

Insights

K-Ras4B protein sustains cell ciliation during differentiation, controlling stem cell commitment. This finding reveals a novel role for K-Ras4B in differentiation and links RASopathies to ciliopathies.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • The Ras-MAPK pathway regulates critical cellular functions like proliferation and differentiation.
  • The precise mechanisms by which Ras proteins control cell differentiation remain incompletely understood.

Purpose of the Study:

  • To elucidate the role of K-Ras4B in skeletal muscle stem and progenitor cell differentiation.
  • To investigate the relationship between K-Ras4B, primary cilia, and cell differentiation.

Main Methods:

  • Mathematical modeling
  • Single-cell RNA sequencing
  • In vivo studies in zebrafish embryogenesis
  • Analysis of protein localization and interactions within primary cilia

Main Results:

  • K-Ras4B sustains primary cilia during differentiation, restricting the commitment of skeletal muscle stem and progenitor cells.
  • Abnormal K-Ras4B levels or oncogenic mutations (K-Ras4B-G12C) disrupt normal differentiation processes.
  • K-Ras4B localizes to primary cilia, where it interacts with components of the MAPK pathway (B-Raf, MEK, ERK).
  • Targeted localization of K-Ras4B to cilia rescues normal differentiation, and in vivo modulation affects ciliation-dependent development.

Conclusions:

  • K-Ras4B plays a fundamental, previously unrecognized role in regulating cell differentiation through the control of primary cilia.
  • This study provides a mechanistic link between RASopathies and ciliopathies, explaining shared phenotypic characteristics.

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