scholarly journals The first buds of Cdc42

2015 ◽  
Vol 209 (6) ◽  
pp. 780-780 ◽  
Author(s):  
Ben Short
Keyword(s):  
Yeast Cell ◽  
Cell Polarization ◽  
Small Gtpase

In 1990, John Pringle and colleagues identified the small GTPase and demonstrated its role in yeast cell polarization.

scholarly journals Activation of Cdc42 GTPase upon CRY2-Induced Cortical Recruitment Is Antagonized by GAPs in Fission Yeast

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2089 ◽  
Author(s):  
Iker Lamas ◽  
Nathalie Weber ◽  
Sophie G. Martin
Keyword(s):  
Fission Yeast ◽  
Positive Feedback ◽  
Antagonistic Activity ◽  
Cell Polarization ◽  
Small Gtpase ◽  
Nucleotide Exchange ◽  
Gtpase Activating Protein ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Cell Architecture

The small GTPase Cdc42 is critical for cell polarization in eukaryotic cells. In rod-shaped fission yeast Schizosaccharomyces pombe cells, active GTP-bound Cdc42 promotes polarized growth at cell poles, while inactive Cdc42-GDP localizes ubiquitously also along cell sides. Zones of Cdc42 activity are maintained by positive feedback amplification involving the formation of a complex between Cdc42-GTP, the scaffold Scd2, and the guanine nucleotide exchange factor (GEF) Scd1, which promotes the activation of more Cdc42. Here, we use the CRY2-CIB1 optogenetic system to recruit and cluster a cytosolic Cdc42 variant at the plasma membrane and show that this leads to its moderate activation also on cell sides. Surprisingly, Scd2, which binds Cdc42-GTP, is still recruited to CRY2-Cdc42 clusters at cell sides in individual deletion of the GEFs Scd1 or Gef1. We show that activated Cdc42 clusters at cell sides are able to recruit Scd1, dependent on the scaffold Scd2. However, Cdc42 activity is not amplified by positive feedback and does not lead to morphogenetic changes, due to antagonistic activity of the GTPase activating protein Rga4. Thus, the cell architecture is robust to moderate activation of Cdc42 at cell sides.

scholarly journals Post-Translational Modification and Subcellular Compartmentalization: Emerging Concepts on the Regulation and Physiopathological Relevance of RhoGTPases

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1990
Author(s):  
Inmaculada Navarro-Lérida ◽  
Miguel Sánchez-Álvarez ◽  
Miguel Ángel del Pozo
Keyword(s):  
Rho Gtpases ◽  
Rho Gtpase ◽  
Protein Complexes ◽  
Specific Protein ◽  
Cell Polarization ◽  
Small Gtpase ◽  
Post Translational Modification ◽  
Functional Regulation ◽  
Subcellular Compartmentalization ◽  
Cellular Compartments

Cells and tissues are continuously exposed to both chemical and physical stimuli and dynamically adapt and respond to this variety of external cues to ensure cellular homeostasis, regulated development and tissue-specific differentiation. Alterations of these pathways promote disease progression—a prominent example being cancer. Rho GTPases are key regulators of the remodeling of cytoskeleton and cell membranes and their coordination and integration with different biological processes, including cell polarization and motility, as well as other signaling networks such as growth signaling and proliferation. Apart from the control of GTP–GDP cycling, Rho GTPase activity is spatially and temporally regulated by post-translation modifications (PTMs) and their assembly onto specific protein complexes, which determine their controlled activity at distinct cellular compartments. Although Rho GTPases were traditionally conceived as targeted from the cytosol to the plasma membrane to exert their activity, recent research demonstrates that active pools of different Rho GTPases also localize to endomembranes and the nucleus. In this review, we discuss how PTM-driven modulation of Rho GTPases provides a versatile mechanism for their compartmentalization and functional regulation. Understanding how the subcellular sorting of active small GTPase pools occurs and what its functional significance is could reveal novel therapeutic opportunities.

scholarly journals The GTP-binding Protein Rho1p Is Required for Cell Cycle Progression and Polarization of the Yeast Cell

1999 ◽  
Vol 146 (2) ◽  
pp. 373-387 ◽  
Author(s):  
Jana Drgonová ◽  
Tomás Drgon ◽  
Dong-Hyun Roh ◽  
Enrico Cabib
Keyword(s):  
Cell Cycle ◽  
Yeast Cell ◽  
Cell Cycle Progression ◽  
Binding Protein ◽  
Cell Polarization ◽  
Nonpermissive Temperature ◽  
Gtp Binding Protein ◽  
Cycle Progression ◽  
Glucan Synthase ◽  
Gtp Binding

Previous work showed that the GTP-binding protein Rho1p is required in the yeast, Saccharomyces cerevisiae, for activation of protein kinase C (Pkc1p) and for activity and regulation of β(1→3)glucan synthase. Here we demonstrate a hitherto unknown function of Rho1p required for cell cycle progression and cell polarization. Cells of mutant rho1E45I in the G1 stage of the cell cycle did not bud at 37°C. In those cells actin reorganization and recruitment to the presumptive budding site did not take place at the nonpermissive temperature. Two mutants in adjacent amino acids, rho1V43T and rho1F44Y, showed a similar behavior, although some budding and actin polarization occurred at the nonpermissive temperature. This was also the case for rho1E45I when placed in a different genetic background. Cdc42p and Spa2p, two proteins that normally also move to the bud site in a process independent from actin organization, failed to localize properly in rho1E45I. Nuclear division did not occur in the mutant at 37°C, although replication of DNA proceeded slowly. The rho1 mutants were also defective in the formation of mating projections and in congregation of actin at the projections in the presence of mating pheromone. The in vitro activity of β(1→3)glucan synthase in rho1 E45I, although diminished at 37°C, appeared sufficient for normal in vivo function and the budding defect was not suppressed by expression of a constitutively active allele of PKC1. Reciprocally, when Pkc1p function was eliminated by the use of a temperature-sensitive mutation and β(1→3)glucan synthesis abolished by an echinocandin-like inhibitor, a strain carrying a wild-type RHO1 allele was able to produce incipient buds. Taken together, these results reveal a novel function of Rho1p that must be executed in order for the yeast cell to polarize.

scholarly journals ATP8B1-mediated spatial organization of Cdc42 signaling maintains singularity during enterocyte polarization

2015 ◽  
Vol 210 (7) ◽  
pp. 1055-1063 ◽  
Author(s):  
Lucas J.M. Bruurs ◽  
Lisa Donker ◽  
Susan Zwakenberg ◽  
Fried J. Zwartkruis ◽  
Harry Begthel ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Apical Membrane ◽  
Membrane Lipids ◽  
Lipid Binding ◽  
Cell Polarization ◽  
Small Gtpase ◽  
Recycling Endosomes ◽  
Charged Membrane ◽  
Polybasic Region ◽  
Control Protein

During yeast cell polarization localization of the small GTPase, cell division control protein 42 homologue (Cdc42) is clustered to ensure the formation of a single bud. Here we show that the disease-associated flippase ATPase class I type 8b member 1 (ATP8B1) enables Cdc42 clustering during enterocyte polarization. Loss of this regulation results in increased apical membrane size with scattered apical recycling endosomes and permits the formation of more than one apical domain, resembling the singularity defect observed in yeast. Mechanistically, we show that to become apically clustered, Cdc42 requires the interaction between its polybasic region and negatively charged membrane lipids provided by ATP8B1. Disturbing this interaction, either by ATP8B1 depletion or by introduction of a Cdc42 mutant defective in lipid binding, increases Cdc42 mobility and results in apical membrane enlargement. Re-establishing Cdc42 clustering, by tethering it to the apical membrane or lowering its diffusion, restores normal apical membrane size in ATP8B1-depleted cells. We therefore conclude that singularity regulation by Cdc42 is conserved between yeast and human and that this regulation is required to maintain healthy tissue architecture.

scholarly journals Rab27 effector Slp2-a transports the apical signaling molecule podocalyxin to the apical surface of MDCK II cells and regulates claudin-2 expression

2012 ◽  
Vol 23 (16) ◽  
pp. 3229-3239 ◽  
Author(s):  
Takao Yasuda ◽  
Chika Saegusa ◽  
Sachiko Kamakura ◽  
Hideki Sumimoto ◽  
Mitsunori Fukuda
Keyword(s):  
Apical Membrane ◽  
Basolateral Membrane ◽  
Cell Polarization ◽  
Small Gtpase ◽  
Apical Surface ◽  
Dependent Manner ◽  
Signaling Molecule ◽  
Downstream Target ◽  
Junction Protein ◽  
Polarized Trafficking

Most cells in tissues are polarized and usually have two distinct plasma membrane domains—an apical membrane and a basolateral membrane, which are the result of polarized trafficking of proteins and lipids. However, the mechanism underlying the cell polarization is not fully understood. In this study, we investigated the involvement of synaptotagmin-like protein 2-a (Slp2-a), an effector molecule for the small GTPase Rab27, in polarized trafficking by using Madin–Darby canine kidney II cells as a model of polarized cells. The results show that the level of Slp2-a expression in MDCK II cells increases greatly as the cells become polarized and that its expression is specifically localized at the apical membrane. The results also reveal that Slp2-a is required for targeting of the signaling molecule podocalyxin to the apical membrane in a Rab27A-dependent manner. In addition, ezrin, a downstream target of podocalyxin, and ERK1/2 are activated in Slp2-a–knockdown cells, and their activation results in a dramatic reduction in the amount of the tight junction protein claudin-2. Because both Slp2-a and claudin-2 are highly expressed in mouse renal proximal tubules, Slp2-a is likely to regulate claudin-2 expression through trafficking of podocalyxin to the apical surface in mouse renal tubule epithelial cells.

scholarly journals ROLE OF SMALL G PROTEINS IN YEAST CELL POLARIZATION AND WALL BIOSYNTHESIS

1998 ◽  
Vol 67 (1) ◽  
pp. 307-333 ◽  
Author(s):  
Enrico Cabib ◽  
Jana Drgonová ◽  
Tomás Drgon
Keyword(s):  
Yeast Cell ◽  
G Proteins ◽  
Cell Polarization ◽  
Small G Proteins

scholarly journals Essential Role of the NH2-Terminal Region of Cdc24 Guanine Nucleotide Exchange Factor in Its Initial Polarized Localization in Saccharomyces cerevisiae

2011 ◽  
Vol 11 (1) ◽  
pp. 2-15 ◽  
Author(s):  
Konomi Fujimura-Kamada ◽  
Tomoe Hirai ◽  
Kazuma Tanaka
Keyword(s):  
Fluorescent Protein ◽  
Cell Polarization ◽  
Small Gtpase ◽  
Terminal Region ◽  
Temperature Sensitive ◽  
Nucleotide Exchange ◽  
Mutant Proteins ◽  
Pb1 Domain ◽  
P21 Activated Kinase ◽  
Green Fluorescent

ABSTRACTThe cortical recruitment and accumulation of the small GTPase Cdc42 are crucial steps in the establishment of polarity, but this process remains obscure. Cdc24 is an upstream regulator of budding yeast Cdc42 that accelerates the exchange of GDP for GTP in Cdc42 via its Dbl homology (DH) domain. Here, we isolated five novel temperature-sensitive (ts)cdc24mutants, the green fluorescent protein (GFP)-fused proteins of which lose their polarized localization at the nonpermissive temperature. All amino acid substitutions in the mutants were mapped to the NH2-terminal region of Cdc24, including the calponin homology (CH) domain. These Cdc24-ts mutant proteins did not interact with Bem1 at the COOH-terminal PB1 domain, suggesting a lack of exposure of the PB1 domain in the mutant proteins. Thecdc24-tsmutants were also defective in polarization in the absence of Bem1. It was previously reported that a fusion protein containing Cdc24 and the p21-activated kinase (PAK)-like kinase Cla4 could bypass the requirement for Bem1 in polarity cue-independent budding (i.e., symmetry breaking). Cdc24-ts–Cla4 fusion proteins also showed ts localization at the polarity site. We propose that the NH2-terminal region unmasks the DH and PB1 domains, leading to the activation of Cdc42 and interaction with Bem1, respectively, to initiate cell polarization.

scholarly journals Cdc42 Is Not Essential for Filopodium Formation, Directed Migration, Cell Polarization, and Mitosis in Fibroblastoid Cells

2005 ◽  
Vol 16 (10) ◽  
pp. 4473-4484 ◽  
Author(s):  
Aleksandra Czuchra ◽  
Xunwei Wu ◽  
Hannelore Meyer ◽  
Jolanda van Hengel ◽  
Timm Schroeder ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Cell Shape ◽  
Cell Polarization ◽  
Small Gtpase ◽  
Dominant Negative ◽  
Directed Migration ◽  
Membrane Blebbing ◽  
Directed Cell Migration ◽  
Rho Family ◽  
Filopodium Formation

Cdc42 is a small GTPase involved in the regulation of the cytoskeleton and cell polarity. To test whether Cdc42 has an essential role in the formation of filopodia or directed cell migration, we generated Cdc42-deficient fibroblastoid cells by conditional gene inactivation. We report here that loss of Cdc42 did not affect filopodium or lamellipodium formation and had no significant influence on the speed of directed migration nor on mitosis. Cdc42-deficient cells displayed a more elongated cell shape and had a reduced area. Furthermore, directionality during migration and reorientation of the Golgi apparatus into the direction of migration was decreased. However, expression of dominant negative Cdc42 in Cdc42-null cells resulted in strongly reduced directed migration, severely reduced single cell directionality, and complete loss of Golgi polarization and of directionality of protrusion formation toward the wound, as well as membrane blebbing. Thus, our data show that besides Cdc42 additional GTPases of the Rho-family, which share GEFs with Cdc42, are involved in the establishment and maintenance of cell polarity during directed migration.

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