K-Ras controls asymmetric cell divisions from the primary cilium.

Authors

Rohan Chippalkatti, Elisabeth Schaffner-Reckinger, Anthoula Gaigneaux, Bianca Parisi, Sara Bottone, Christina Laurini, Yashar Rouzbahani, Mariska Dijkers, Atanasio Gómez-Mulas, Thomas Sauter, Jeroen den Hertog, Christian Eggeling, Daniel Kwaku Abankwa

Published in

Cell death & disease. Jul 11, 2026. Epub Jul 11, 2026.

Abstract

The Ras-MAPK pathway drives central cellular processes, including cell proliferation and differentiation. How exactly Ras controls differentiation is however not understood. Supported by mathematical modeling and single-cell RNA sequencing we show that K-Ras4B sustains ciliation during differentiation thus restricting commitment of skeletal muscle stem and progenitor cells during asymmetric cell divisions. Modulation of K-Ras4B abundance or expression of oncogenic K-Ras4B-G12C perturb normal differentiation. K-Ras4B, but not N-Ras and H-Ras, localizes to the primary cilium and its abundance there depends on the ciliary trafficking chaperone PDE6D. The presence of B-Raf and active MEK at the base of and active ERK inside the cilium suggests that K-Ras4B is active there. Conditions that localize a K-Ras4B mutant only to the cilium are sufficient to sustain ciliation and normal differentiation. Finally, in vivo modulation of K-Ras4B activity during zebrafish embryogenesis perturbs ciliation-dependent heart-looping. Our results thus imply a novel fundamental role of K-Ras4B in controlling ciliation and differentiation and suggest an explanation for the phenotypic similarities between RASopathies and ciliopathies.

PMID:
42436151
Bibliographic data and abstract were imported from PubMed on 12 Jul 2026.

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