TY - JOUR
T1 - Conserved NDR/LATS kinase controls RAS GTPase activity to regulate cell growth and chronological lifespan
AU - Chen, Chuan
AU - Pino, Marbelys Rodriguez
AU - Haller, Patrick Roman
AU - Verde, Fulvia
N1 - Funding Information:
We thank Sophie G. Martin (University of Lausanne, Lausanne, Switzerland) and Arun Malhotra (University of Miami, Miami, FL) for providing strains and plasmids. We thank Sandra Lemmon (University of Miami, Miami, FL) and Maitreyi Das (University of Tennessee, Knoxville, TN) for critical review of the manuscript. We thank April Mann (University of Miami, Miami, FL) for comments on the manuscript. We thank Qin Yang (University of Miami, Miami, FL) for technical support in data visualization. This work in F.V.'s laboratory was supported by National Institutes of Health R01 Grant GM095867 and by the Sylvester Comprehensive Cancer Center.
Funding Information:
We thank Sophie G. Martin (University of Lausanne, Lausanne, Switzerland) and Arun Malhotra (University of Miami, Miami, FL) for providing strains and plasmids. We thank Sandra Lemmon (University of Miami, Miami, FL) and Maitreyi Das (University of Tennessee, Knoxville, TN) for critical review of the manuscript. We thank April Mann (University of Miami, Miami, FL) for comments on the manuscript. We thank Qin Yang (University of Miami, Miami, FL) for technical support in data visualization. This work in F.V.’s laboratory was supported by National Institutes of Health R01 Grant GM095867 and by the Sylvester Comprehensive Cancer Center.
Publisher Copyright:
© 2019 Chen et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution-Noncommercial-Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
PY - 2019/9/15
Y1 - 2019/9/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85072546365&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85072546365&partnerID=8YFLogxK
U2 - 10.1091/mbc.E19-03-0172
DO - 10.1091/mbc.E19-03-0172
M3 - Article
C2 - 31390298
AN - SCOPUS:85072546365
VL - 30
SP - 2598
EP - 2616
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
SN - 1059-1524
IS - 20
ER -