K-Ras controls asymmetric cell divisions from the primary cilium

in: Cell Death and Disease (2026)
Chippalkatti, Rohan; Schaffner-Reckinger, Elisabeth; Gaigneaux, Anthoula; Parisi, Bianca; Bottone, Sara; Laurini, Christina; Rouzbahani, Yashar; Dijkers, Mariska; Gómez-Mulas, Atanasio; Sauter, Thomas; Hertog, den Jeroen; Eggeling, Christian; Abankwa, Daniel
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.

Cookies & Skripte von Drittanbietern

Diese Website verwendet Cookies. Für eine optimale Performance, eine reibungslose Verwendung sozialer Medien und aus Werbezwecken empfiehlt es sich, der Verwendung von Cookies & Skripten durch Drittanbieter zuzustimmen. Dafür werden möglicherweise Informationen zu Ihrer Verwendung der Website von Drittanbietern für soziale Medien, Werbung und Analysen weitergegeben.
Weitere Informationen finden Sie unter Datenschutz und im Impressum.
Welchen Cookies & Skripten und der damit verbundenen Verarbeitung Ihrer persönlichen Daten stimmen Sie zu?

Sie können Ihre Einstellungen jederzeit unter Datenschutz ändern.