Conserved NDR/LATS kinase controls RAS GTPase activity to regulate cell growth and chronological lifespan

Molecular Biology of the Cell
Chuan ChenFulvia Verde

Abstract

Adaptation to the nutritional environment is critical for all cells. RAS GTPase is a highly conserved GTP-binding protein with crucial functions for cell growth and differentiation in response to environmental conditions. Here, we describe a novel mechanism connecting RAS GTPase to nutrient availability in fission yeast. We report that the conserved NDR/LATS kinase Orb6 responds to nutritional cues and regulates Ras1 GTPase activity. Orb6 increases the protein levels of an Ras1 GTPase activator, the guanine nucleotide exchange factor Efc25, by phosphorylating Sts5, a protein bound to efc25 mRNA. By manipulating the extent of Orb6-mediated Sts5 assembly into RNP granules, we can modulate Efc25 protein levels, Ras1 GTPase activity, and, as a result, cell growth and cell survival. Thus, we conclude that the Orb6-Sts5-Ras1 regulatory axis plays a crucial role in promoting cell adaptation, balancing the opposing demands of promoting cell growth and extending chronological lifespan.

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Citations

May 13, 2021·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Hokuto OhtsukaHirofumi Aiba
Jul 21, 2021·ELife·Joseph O Magliozzi, James B Moseley

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Methods Mentioned

BETA
GTPases
GTPase
nucleotide
nucleotide exchange
pull down
pull-down
immunodepletion
affinity purification

Software Mentioned

GraphPad Prism
SPSS Statistics
Fiji
VSL2B
ImageJ
VLXT
Intelligent Imaging Innovations SlideBook
PONDR
R
readxl

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