The longevity of tor1Δ, sch9Δ, and ras2Δ mutants depends on actin dynamics in Saccharomyces cerevisiae

Cell & Bioscience

Shengnan Meng¹  Qiang Bi²  Didi Wu²  Nanqi Liu²  Ying Liu² 

[1] Department of Pharmaceutics, Pharmacy school of China Medical University, Shenyang 110001, P. R. China;Department of Biochemistry and Molecular Biology, Key Laboratory of Cell Biology, Ministry of Public Health, China Medical University, Shenyang, P. R. China

关键词: Actin dynamic;    Longevity;    Ras2;    Sch9;    Tor1;   

Others  :  1220353
DOI  :  10.1186/s13578-015-0008-z

 received in 2014-11-23, accepted in 2015-03-31,  发布年份 2015

【 摘 要 】

Recent studies have revealed the role of actin dynamics in the regulation of yeast aging. Although the target of rapamycin (TOR) complex, serine/threonine kinase Sch9, and Ras2 have been shown to play important roles in aging for a long time, the relationship between these regulators and actin has not yet been reported. In this study we investigated the roles of actin polarization in tor1Δ, sch9Δ, and ras2Δ mutant cells. We found that the actin structures in tor1Δ, sch9Δ, and ras2Δ mutant cells were more dynamic than those in the wild type. Destruction of the actin structures with jasplakinolide decreased the life span of tor1Δ, sch9Δ, and ras2Δ mutants. Furthermore, deletion of SLA1 in tor1Δ, sch9Δ, and ras2Δ mutants inhibited the actin dynamics and life span. In addition, we found that the actin cytoskeleton of the long-lived mutant sch9Δ, depended on the transcription factors RIM15 and MSN2/4, but not GIS1, while the actin skeleton of the tor1Δ and ras2Δ mutants depended on RIM15 as expected. Our data suggest that the longevity of tor1Δ, sch9Δ, and ras2Δ mutants is dependent on actin dynamics.

【 授权许可】

   
2015 Liu et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Mortimer RK, Johnston JR. Life span of individual yeast cells. Nature. 1959; 183:1751-2.
• [2]Lavoie H, Whiteway M. Increased respiration in the sch9 Delta mutant is required for increasing chronological life span but not replicative life span. Eukaryot Cell. 2008; 7:1127-35.
• [3]Fabrizio P, Longo VD. The chronological life span of Saccharomyces cerevisiae. Aging Cell. 2003; 2:73-81.
• [4]Cornu M, Albert V, Hall MN. mTOR in aging, metabolism, and cancer. Curr Opin Genet Dev. 2013; 23:53-62.
• [5]Bonawitz ND, Chatenay-Lapointe M, Pan Y, Shadel GS. Reduced TOR signaling extends chronological life span via increased respiration and upregulation of mitochondrial gene expression. Cell Metab. 2007; 5:265-77.
• [6]Pan Y, Shadel GS. Extension of chronological life span by reduced TOR signaling requires down-regulation of Sch9p and involves increased mitochondrial OXPHOS complex density. Aging. 2009; 1:131-45.
• [7]Schieke SM, Finkel T. TOR and aging: less is more. Cell Metab. 2007; 5:233-5.
• [8]Kandel ES, Hay N. The regulation and activities of the multifunctional serine/threonine kinase Akt/PKB. Exp Cell Res. 1999; 253:210-29.
• [9]Thevelein JM, de Winde JH. Novel sensing mechanisms and targets for the cAMP-protein kinase A pathway in the yeast Saccharomyces cerevisiae. Mol Microbiol. 1999; 33:904-18.
• [10]Urban J, Soulard A, Huber A, Lippman S, Mukhopadhyay D, Deloche O et al.. Sch9 is a major target of TORC1 in Saccharomyces cerevisiae. Mol Cell. 2007; 26:663-74.
• [11]Fabrizio P, Pozza F, Pletcher SD, Gendron CM, Longo VD. Regulation of longevity and stress resistance by Sch9 in yeast. Science. 2001; 292:288-90.
• [12]Wei M, Fabrizio P, Hu J, Ge HY, Cheng C, Li L et al.. Life span extension by calorie restriction depends on Rim15 and transcription factors downstream of Ras/PKA, Tor, and Sch9. PLoS Genet. 2008; 4:139-49.
• [13]Gourlay CW, Carpp LN, Timpson P, Winder SJ, Ayscough KR. A role for the actin cytoskeleton in cell death and aging in yeast. J Cell Biol. 2004; 164:803-9.
• [14]Gourlay CW, Ayscough KR. A role for actin in aging and apoptosis. Biochem Soc Trans. 2005; 33:1260-4.
• [15]Warren DT, Andrews PD, Gourlay CW, Ayscough KR. Sla1p couples the yeast endocytic machinery to proteins regulating actin dynamics. J Cell Sci. 2002; 115:1703-15.
• [16]Ayscough KR. Endocytosis and the development of cell polarity in yeast require a dynamic F-actin cytoskeleton. Curr Biol. 2000; 10:1587-90.
• [17]Wei M, Fabrizio P, Madia F, Hu J, Ge HY, Li LM et al.. Tor1/Sch9-regulated carbon source substitution is as effective as calorie restriction in life span extension. PLoS Genet. 2009; 5: Article ID e1000467
• [18]Torres J, Di Como CJ, Herrero E, De La Torre-Ruiz MA. Regulation of the cell integrity pathway by rapamycin-sensitive TOR function in budding yeast. J Biol Chem. 2002; 277:43495-504.
• [19]Ho J, Bretscher A. Ras regulates the polarity of the yeast actin cytoskeleton through the stress response pathway. Mol Biol Cell. 2001; 12:1541-55.
• [20]Gourlay CW, Ayscough KR. Actin-induced hyperactivation of the Ras signaling pathway leads to apoptosis in Saccharomyces cerevisiae. Mol Cell Biol. 2006; 26:6487-501.
• [21]Swinnen E, Wilms T, Idkowiak-Baldys J, Smets B, De Snijder P, Accardo S et al.. The protein kinase Sch9 is a key regulator of sphingolipid metabolism in Saccharomyces cerevisiae. Mol Biol Cell. 2014; 25:196-211.
• [22]Dickson RC. Roles for sphingolipids in Saccharomyces cerevisiae. Adv Exp Med Biol. 2010; 688:217-31.
• [23]Sherman F. Getting started with yeast. Methods Enzymol. 2002; 350:3-41.
• [24]Longtine MS, McKenzie A, Demarini DJ, Shah NG, Wach A, Brachat A et al.. Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae. Yeast. 1998; 14:953-61.
• [25]Parrella E, Longo VD. The chronological life span of Saccharomyces cerevisiae to study mitochondrial dysfunction and disease. Methods. 2008; 46:256-62.
• [26]Madeo F, Frohlich E, Ligr M, Grey M, Sigrist SJ, Wolf DH et al.. Oxygen stress: a regulator of apoptosis in yeast. J Cell Biol. 1999; 145:757-67.