Scholarlink

<p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

K-Ras controls asymmetric cell divisions from the primary cilium

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月11日

查看全文
  • 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

摘要

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.