Mechanisms for concentrating Rho1 during cytokinesis

Parkinson disease (PD) results from the slow, progressive loss of dopaminergic neurons in the substantia nigra. Alterations in α-synuclein (aSyn), such as mutations or multiplications of the gene, are thought to trigger this degeneration. Here, we show that aSyn disrupts mitogen-activated protein kinase (MAPK)-controlled stress signaling in yeast and human cells, which results in inefficient cell protective responses and cell death. aSyn is a substrate of the yeast (and human) polo-like kinase Cdc5 (Plk2), and elevated levels of aSyn prevent Cdc5 from maintaining a normal level of GTP-bound Rho1, which is an essential GTPase that regulates stress signaling. The nine N-terminal amino acids of aSyn are essential for the interaction with polo-like kinases. The results support a unique mechanism of PD pathology.aging | neurodegeneration | proteinopathy

show abstract

“…S3B). SAC7 encodes a Rho1 GAP, and deletion of this gene increases the total cellular level of GTP-Rho1 (20).…”

Section: Resultsmentioning

confidence: 99%

α-Synuclein disrupts stress signaling by inhibiting polo-like kinase Cdc5/Plk2

Wang

Liou

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Rho1 is thought to promote actin ring assembly by activating the formin Bni1 [Tolliday et al, 2002]. The localization and activation of Rho1 at the division site is, in turn, controlled by its guanine-nucleotide-exchange factor (GEF), which is regulated by the Polo kinase Cdc5 [Yoshida et al, 2006[Yoshida et al, , 2009. This cascade of activation-coupled protein recruitment to the division site defines a mechanism for the cell cycle control of actin ring assembly.…”

Section: Amr Assemblymentioning

confidence: 99%

Mechanisms of cytokinesis in budding yeast

Wloka

2012

Cytoskeleton

View full text Add to dashboard Cite

Cytokinesis is essential for cell proliferation in all domains of life. Because the core components and mechanisms of cytokinesis are conserved from fungi to humans, the budding yeast Saccharomyces cerevisiae has served as an attractive model for studying this fundamental process. Cytokinesis in budding yeast is driven by two interdependent cellular events: actomyosin ring (AMR) constriction and the formation of a chitinous cell wall structure called the primary septum (PS), the functional equivalent of extracellular matrix remodeling during animal cytokinesis. AMR constriction is thought to drive efficient plasma membrane ingression as well as to guide PS formation, whereas PS formation is thought to stabilize the AMR during its constriction. Following the completion of the PS formation, two secondary septa (SS), consisting of glucans and mannoproteins, are synthesized at both sides of the PS. Degradation of the PS and a part of the SS by a chitinase and glucanases then enables cell separation. In this review, we discuss the mechanics of cytokinesis in budding yeast, highlighting its common and unique features as well as the emerging questions. © 2012 Wiley Periodicals, Inc.

show abstract

“…Does Tus1 activate Rho1 on the vacuolar membrane? Rho1 localizes to the plasma membrane and to other sites including bud tips, the mother-bud neck, and endomembranes (McCaffrey et al 1991;Drgonova et al 1996;Qadota et al 1996;Yoshida et al 2009), while Ycf1 localizes to the vacuolar membrane (Wemmie and Moye-Rowley 1997;Mason and Michaelis 2002). Tus1 localizes to the presumptive bud site in unbudded cells and to the mother-bud neck during cytokinesis (Yoshida et al 2006;Kono et al 2008), but has not been observed on the vacuolar membrane.…”

mentioning

confidence: 99%

The Rho1 GTPase Acts Together With a Vacuolar Glutathione S-Conjugate Transporter to Protect Yeast Cells From Oxidative Stress

Lee

Singh²,

Snider

et al. 2011

Genetics

View full text Add to dashboard Cite

Maintenance of redox homeostasis is critical for the survival of all aerobic organisms. In the budding yeast Saccharomyces cerevisiae, as in other eukaryotes, reactive oxygen species (ROS) are generated during metabolism and upon exposure to environmental stresses. The abnormal production of ROS triggers defense mechanisms to avoid the deleterious consequence of ROS accumulation. Here, we show that the Rho1 GTPase is necessary to confer resistance to oxidants in budding yeast. Temperature-sensitive rho1 mutants (rho1 ts ) are hypersensitive to oxidants and exhibit high accumulation of ROS even at a semipermissive temperature. Rho1 associates with Ycf1, a vacuolar glutathione S-conjugate transporter, which is important for heavy metal detoxification in yeast. Rho1 and Ycf1 exhibit a two-hybrid interaction with each other and form a bimolecular fluorescent complex on the vacuolar membrane. A fluorescent-based complementation assay suggests that the GTP-bound Rho1 associates with Ycf1 and that their interaction is enhanced upon exposure to hydrogen peroxide. The rho1 ts mutants also exhibit hypersensitivity to cadmium, while cells carrying a deletion of YCF1 or mutations in a component of the Pkc1-MAP kinase pathway exhibit little or minor sensitivity to oxidants. We thus propose that Rho1 protects yeast cells from oxidative stress by regulating multiple downstream targets including Ycf1. Since both Rho1 and Ycf1 belong to highly conserved families of proteins, similar mechanisms may exist in other eukaryotes.

show abstract

Mechanisms for concentrating Rho1 during cytokinesis

Cited by 126 publications

References 61 publications

α-Synuclein disrupts stress signaling by inhibiting polo-like kinase Cdc5/Plk2

α-Synuclein disrupts stress signaling by inhibiting polo-like kinase Cdc5/Plk2

Mechanisms of cytokinesis in budding yeast

The Rho1 GTPase Acts Together With a Vacuolar Glutathione S-Conjugate Transporter to Protect Yeast Cells From Oxidative Stress

Contact Info

Product

Resources

About