Rho1p, a Yeast Protein at the Interface Between Cell Polarization and Morphogenesis

Drgonová, Jana; Drgon, Tomás; Tanaka, Kazuma; Kollár, R.; Chen, Guang Chao; Ford, R.A.; Chan, Chung Chow; Takai, Yoshimi; Cabib, Enrico

doi:10.1126/science.272.5259.277

Cited by 319 publications

(280 citation statements)

References 21 publications

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“…Nevertheless, the results described herein are sufficient to indicate that Cla4 is the first known effector of the plasma membrane pool of PI4P generated by Stt4. In contrast, Rom2, a guanine nucleotide exchange factor for Rho1 that regulates yeast cell wall biosynthesis and integrity (61), is an effector of PI4,5P2 (20).…”

Section: Discussionmentioning

confidence: 99%

The p21-activated Protein Kinase-related Kinase Cla4 Is a Coincidence Detector of Signaling by Cdc42 and Phosphatidylinositol 4-Phosphate

Wild

Lemmon

et al. 2004

Journal of Biological Chemistry

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Signal transduction pathways that co-regulate a given biological process often are organized into networks by molecules that act as coincidence detectors. Phosphoinositides and the Rho-type GTPase Cdc42 regulate overlapping processes in all eukaryotic cells. However, the coincidence detectors that link these pathways into networks remain unknown. Here we show that the p21-activated protein kinase-related kinase Cla4 of yeast integrates signaling by Cdc42 and phosphatidylinositol 4-phosphate (PI4P). We found that the Cla4 pleckstrin homology (PH) domain binds in vitro to several phosphoinositide species. To determine which phosphoinositides regulate Cla4 in vivo, we analyzed phosphatidylinositol kinase mutants (stt4, mss4, and pik1). This indicated that the plasma membrane pool of PI4P, but not phosphatidylinositol 4,5-bisphosphate or the Golgi pool of PI4P, is required for localization of Cla4 to sites of polarized growth. A combination of the Cdc42-binding and PH domains of Cla4 was necessary and sufficient for localization to sites of polarized growth. Point mutations affecting either domain impaired the ability of Cla4 to regulate cell morphogenesis and the mitotic exit network (localization of Lte1). Therefore, Cla4 must retain the ability to bind both Cdc42 and phosphoinositides, the hallmark of a coincidence detector. PI4P may recruit Cla4 to the plasma membrane where Cdc42 activates its kinase activity and refines its localization to cortical sites of polarized growth. In mammalian cells, the myotonic dystrophy-related Cdc42-binding kinase possesses p21-binding and PH domains, suggesting that this kinase may be a coincidence detector of signaling by Cdc42 and phosphoinositides.

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Section: Discussionmentioning

confidence: 99%

The p21-activated Protein Kinase-related Kinase Cla4 Is a Coincidence Detector of Signaling by Cdc42 and Phosphatidylinositol 4-Phosphate

Wild

Lemmon

et al. 2004

Journal of Biological Chemistry

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“…␤-1,3-Glucan is synthesized by ␤-1,3-glucan synthase (GS) localized on the plasma membrane (Qadota et al, 1996). GS is composed of a catalytic subunit encoded by the two homologous genes FKS1 and FKS2 (Inoue et al, 1995;Mazur et al, 1995), and a regulatory subunit, the small GTPase, Rho1p (Drgonova et al, 1996;Qadota et al, 1996). The Rho-type GTPase is generally regulated by switching between a GDPbound inactive state and a GTP-bound active state (Wei et al, 1997;Ihara et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Loss of Function ofKRE5Suppresses Temperature Sensitivity of Mutants Lacking Mitochondrial Anionic Lipids

Zhong

Gvozdenović-Jeremić

Webster

et al. 2005

MBoC

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Disruption of PGS1, which encodes the enzyme that catalyzes the committed step of cardiolipin (CL) synthesis, results in loss of the mitochondrial anionic phospholipids phosphatidylglycerol (PG) and CL. The pgs1⌬ mutant exhibits severe growth defects at 37°C. To understand the essential functions of mitochondrial anionic lipids at elevated temperatures, we isolated suppressors of pgs1⌬ that grew at 37°C. One of the suppressors has a loss of function mutation in KRE5, which is involved in cell wall biogenesis. The cell wall of pgs1⌬ contained markedly reduced ␤-1,3-glucan, which was restored in the suppressor. Stabilization of the cell wall with osmotic support alleviated the cell wall defects of pgs1⌬ and suppressed the temperature sensitivity of all CL-deficient mutants. Evidence is presented suggesting that the previously reported inability of pgs1⌬ to grow in the presence of ethidium bromide was due to defective cell wall integrity, not from "petite lethality." These findings demonstrated that mitochondrial anionic lipids are required for cellular functions that are essential in cell wall biogenesis, the maintenance of cell integrity, and survival at elevated temperature. INTRODUCTIONCardiolipin (CL), a unique anionic phospholipid with dimeric structure, is ubiquitous in eukaryotes and primarily found in the mitochondrial inner membrane . CL plays a key role in mitochondrial bioenergetics (Jiang et al., 2000; Greenberg, 2000, 2002;Schlame et al., 2000;Pfeiffer et al., 2003) and is also involved in mitochondrial biogenesis (Kawasaki et al., 1999;Jiang et al., 2000). Defective remodeling of CL is associated with Barth syndrome, a severe genetic disorder characterized by cardiomyopathy, neutropenia, skeletal myopathy, and respiratory chain defects (Vreken et al., 2000). The phenotype of Barth syndrome is dependent upon multiple factors that are not well understood (Barth et al., 1983(Barth et al., , 1996. Elucidation of the functions of CL will help to clarify the abnormalities associated with this disorder.The biosynthesis of CL is conserved in eukaryotic organisms. It occurs via three enzymatic reactions , including formation of phosphatidylglycerolphosphate (PGP) from CDP-DAG and glycerol-3-P, dephosphorylation of PGP to phosphatidylglycerol (PG), and condensation of CDP-DAG and PG to form CL. Disruption of PGS1, the structural gene encoding PGP synthase, results in the complete loss of both PG and CL (Janitor et al., 1996;Chang et al., 1998a). The crd1⌬ mutant, which lacks CL synthase, has no detectable CL but accumulates PG (Jiang et al., 1997;Chang et al., 1998b;Tuller et al., 1998;Jiang et al., 2000;Pfeiffer et al., 2003;Zhong et al., 2004). The human taffazin gene (TAZ1), which is associated with Barth syndrome, encodes a transacylase that may be involved in the remodeling of CL (Xu et al., 2003). Deletion of the yeast homolog of this gene, TAZ1, leads to decreased CL, aberrant CL acyl species, and accumulation of monolysocardiolipin . Mutants deficient in CL biosynthesis exhibit growth defects at elevat...

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“…Actin colocalizes with the site of new cell wall deposition at the growing hyphal tip in filamentous fungi and at the bud tip in yeast. In yeast the small GTP protein Rholp that activates glucan synthesis colocalizes with actin at the bud tip (Yamochi et al, 1994;Bussey, 1996;Drgonova et al, 1996;Quadota et al, 1996). Mutations affecting the actin cytoskeleton and myosin cause cell rounding and (Read et al, 1992;McGoldrick et al, 1995;Goodson et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Deletion of nudC, a nuclear migration gene of Aspergillus nidulans, causes morphological and cell wall abnormalities and is lethal.

Chiu¹,

Xiang²,

Dawe³

et al. 1997

MBoC

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Nuclear migration is required for normal development in both higher and lower eukaryotes. In fungi this process is mediated by cytoplasmic dynein. It is believed that this motor protein is anchored to the cell membrane and moves nuclei by capturing and pulling on spindle pole body microtubules. To date, four genes have been identified and shown to be required for this process in Aspergillus nidulans. The nudA and nudG genes, respectively, encode the heavy and light chains of cytoplasmic dynein, and the nudF and nudC gene products encode proteins of 49 and 22 kDa. The precise biochemical functions of the nudF and nudC genes have not yet been identified. In this report we further investigate NUDC protein function by deleting the nudC gene. Surprisingly, although deletion of nudA and nudF affect nuclear migration, deletion of nudC profoundly affected the morphology and composition of the cell wall. Spores of the strain deleted for nudC grew spherically and lysed. The thickness of the cell wall was increased in the deletion mutant and wall polymer composition was abnormal. This phenotype could be repressed by growth on osmotically buffered medium at low temperature. Similar, but less severe, effects were also noted in a strain depleted for NUDC by down-regulation. These results suggest a possible relationship between fungal cell wall biosynthesis and nuclear migration.

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Rho1p, a Yeast Protein at the Interface Between Cell Polarization and Morphogenesis

Cited by 319 publications

References 21 publications

The p21-activated Protein Kinase-related Kinase Cla4 Is a Coincidence Detector of Signaling by Cdc42 and Phosphatidylinositol 4-Phosphate

The p21-activated Protein Kinase-related Kinase Cla4 Is a Coincidence Detector of Signaling by Cdc42 and Phosphatidylinositol 4-Phosphate

Loss of Function ofKRE5Suppresses Temperature Sensitivity of Mutants Lacking Mitochondrial Anionic Lipids

Deletion of nudC, a nuclear migration gene of Aspergillus nidulans, causes morphological and cell wall abnormalities and is lethal.

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