Bni1p, a Yeast Formin Linking Cdc42p and the Actin Cytoskeleton During Polarized Morphogenesis

Evangelista, Marie; Blundell, Kelly; Longtine, Mark S.; Chow, Clinton J.; Adames, Neil R.; Pringle, John R.; Peter, Matthias; Boone, Charles

doi:10.1126/science.276.5309.118

Cited by 614 publications

(669 citation statements)

References 42 publications

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“…The interaction of TC10 with pro®lin may provide valuable insights into mechanisms linking cytoskeletal rearrangements to the Rho family. For example, the recent observations that budding yeast Cdc42p and Rho1p, required for actin cytoskeletal reorganization during bud site initiation and growth, respectively, bind to Bni1p and that Bni1p is itself a pro®lin-binding protein that participates in cell polarization (Kohno et al, 1996;Evangelista et al, 1997), suggest both that additional links may exist and that pro®lin may play a key role in all of them. We expect that a biochemical and functional characterization of the TC10 GTPase and its interactions with pro®lin may provide insight into general features of the links that couple Rho family GTPases to the cellular state of the actin cytoskeleton and to the processes that control cell cycle progression.…”

Section: Discussionmentioning

confidence: 99%

Cellular functions of TC10, a Rho family GTPase: regulation of morphology, signal transduction and cell growth

Murphy

Solski²,

Jillian

et al. 1999

Oncogene

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The small Ras-related GTPase, TC10, has been classi®ed on the basis of sequence homology to be a member of the Rho family. This family, which includes the Rho, Rac and CDC42 subfamilies, has been shown to regulate a variety of apparently diverse cellular processes such as actin cytoskeletal organization, mitogen-activated protein kinase (MAPK) cascades, cell cycle progression and transformation. In order to begin a study of TC10 biological function, we expressed wild type and various mutant forms of this protein in mammalian cells and investigated both the intracellular localization of the expressed proteins and their abilities to stimulate known Rho family-associated processes. Wild type TC10 was located predominantly in the cell membrane (apparently in the same regions as actin ®laments), GTPase defective (75L) and GTP-binding defective (31N) mutants were located predominantly in cytoplasmic perinuclear regions, and a deletion mutant lacking the carboxyl terminal residues required for posttranslational prenylation was located predominantly in the nucleus. The GTPase defective (constitutively active) TC10 mutant: (1) stimulated the formation of long ®lopodia; (2) activated c-Jun amino terminal kinase (JNK); (3) activated serum response factor (SRF)-dependent transcription; (4) activated NF-kB-dependent transcription; and (5) synergized with an activated Rafkinase (Raf-CAAX) to transform NIH3T3 cells. In addition, wild type TC10 function is required for full HRas transforming potential. We demonstrate that an intact e ector domain and carboxyl terminal prenylation signal are required for proper TC10 function and that TC10 signals to at least two separable downstream target pathways. In addition, TC10 interacted with the actin-binding and ®lament-forming protein, pro®lin, in both a two-hybrid cDNA library screen, and an in vitro binding assay. Taken together, these data support a classi®cation of TC10 as a member of the Rho family, and in particular, suggest that TC10 functions to regulate cellular signaling to the actin cytoskeleton and processes associated with cell growth.

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Section: Discussionmentioning

confidence: 99%

Cellular functions of TC10, a Rho family GTPase: regulation of morphology, signal transduction and cell growth

Murphy

Solski²,

Jillian

et al. 1999

Oncogene

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Section: Introductionmentioning

confidence: 99%

“…The FH1 region is a proline-rich stretch that recruits profilin, an actin-monomer binding protein essential for formin function in vivo , to participate in FH2-mediated nucleation in vitro (Sagot et al, 2002b;Kovar et al, 2003;Pring et al, 2003). Other regions present in Bni1p and Bnr1p are a regulatory NH 2 -terminal rho-GTPase-binding domain that subjects many formins to rho-dependent activation (Kohno et al, 1996;Evangelista et al, 1997;Imamura et al, 1997;Dong et al, 2003), and an FH3 motif that helps localize formins within the cell (Petersen et al, 1998).With loss of formin function, actin cables disassemble in 2 min, and a cytokinetic ring is unable to assemble, but actin patches remain intact Sagot et al, 2002a;Tolliday et al, 2002). Other actin nucleators, particularly the Arp2/3 complex, play no apparent role in cable or cytokinetic ring assembly in budding yeast (Winter et al, 1999;Evangelista et al, 2002;Tolliday et al, 2002), suggesting the formins might be in vivo nucleators for these actin filaments.…”

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confidence: 99%

“…As has been seen for similar Bni1p-derived constructs, this construct stimulated the polymerization of actin from monomers, whereas GST did not. Thus, the conserved COOH-terminal regions of the two yeast formins stimulate actin assembly.Based on studies of overexpressed Bni1p and Bnr1p, the NH 2 termini of these formins help confer distinct localizations on the two (Jansen et al, 1996;Evangelista et al, 1997;Fujiwara et al, 1998;Kamei et al, 1998;Ozaki-Kuroda et al, 2001). We wished to examine whether these localizations impart differences in the distribution of the actin filaments assembled by the two isoforms.…”

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confidence: 99%

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Stable and Dynamic Axes of Polarity Use Distinct Formin Isoforms in Budding Yeast

Pruyne

Gao

et al. 2004

MBoC

151

208

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Bud growth in yeast is guided by myosin-driven delivery of secretory vesicles from the mother cell to the bud. We find transport occurs along two sets of actin cables assembled by two formin isoforms. The Bnr1p formin assembles cables that radiate from the bud neck into the mother, providing a stable mother-bud axis. These cables also depend on septins at the neck and are required for efficient transport from the mother to the bud. The Bni1p formin assembles cables that line the bud cortex and target vesicles to varying locations in the bud. Loss of these cables results in morphological defects as vesicles accumulate at the neck. Assembly of these cables depends on continued polarized secretion, suggesting vesicular transport provides a positive feedback signal for Bni1p activation, possibly by rho-proteins. By coupling different formin isoforms to unique cortical landmarks, yeast uses common cytoskeletal elements to maintain stable and dynamic axes in the same cell. INTRODUCTIONProper cell polarization requires a balance between dynamism and stability. Persistent systems, such as the apical and basolateral domains of epithelial cells, show a higher stability than flexible systems, such as cells undergoing chemotaxis. However, both types can use similar cytoskeletal components, so an important task in understanding the control of polarity is to identify features that influence persistence, and how those features integrate with the core cytoskeletal machinery providing the physical expression of polarity.The process of bud growth of the yeast Saccharomyces cerevisiae provides a model for examining the control of polarity (for reviews, see Bretscher, 2003;Chang and Peter, 2003). Secretory organelles, such as the Golgi and endoplasmic reticulum, are distributed throughout the bud and mother cell, whereas post-Golgi secretory vesicles concentrate at discrete growth sites at the cell cortex. These vesicles are guided to these sites along what are essentially two axes of polarity: a stable axis directing traffic from the mother into the bud, and a dynamic axis that fine-tunes delivery from the bud neck to specific regions in the bud, sending vesicles first to the small bud tip, then to the entire bud surface, and finally back toward the neck during mother/daughter separation. On delivery to these locations, post-Golgi vesicles fuse with the cell surface to promote localized cell expansion.Two class-V myosins, with heavy chains encoded by MYO2 (Johnston et al., 1991) and MYO4 (Haarer et al., 1994), propel cellular components, including vesicles, organelles, mRNAs, and microtubules, from the mother into the bud during growth and organelle segregation. The myosins move along cables of actin filaments that radiate throughout the cell in arrays oriented toward growth sites (Adams and Pringle, 1984;Kilmartin and Adams, 1984).Assembly of these cables depends on two formin homologues, Bni1p and Bnr1p (Evangelista et al., 2002;Sagot et al., 2002a), members of a family of cytoskeletal regulatory proteins defined by conserved fo...

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“…When cells response to pheromone, the process of polarized growth requires activation of the cell integrity pathway and Mpk1p activation during pheromone induction requires the transcriptional output of the mating-pheromone response pathway [6,9]. Spa2p, Bni1p and Pea2p are proposed to act together as a complex termed polarisome to establish cell polarity [10][11][12][13][14][15][16]. Spa2p, Bni1p and Pea2p localize at the shmoo tip in response to pheromone [11,13,[17][18][19] and are proposed to mediate crosstalks between the mating-pheromone response pathway and the cell integrity pathway [16].…”

Section: Introductionmentioning

confidence: 99%

Afr1p has a role in regulating the localization of Mpk1p at the shmoo tip in Saccharomyces cerevisiae

2007

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Afr1p functions to promote adaptation to pheromoneinduced growth arrest and morphogenesis. We show here that Afr1p regulates polarized localization of the Mpk1p MAP kinase in shmooing cells. Deletion of AFR1 results in mislocalization of Mpk1p although the scaffold protein Spa2p localizes normally at shmoo tip, and overexpression of Spa2 cannot rescue this defect, indicating Afr1p in required for Spa2p to recruit Mpk1 to the site of polarized growth during mating. Overexpression of SPA2 partially suppresses the morphogenetic defect of afr1D cells upon a-factor induction, suggesting the two proteins function in the same genetic pathway with Spa2p acts downstream of Afr1p.

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Bni1p, a Yeast Formin Linking Cdc42p and the Actin Cytoskeleton During Polarized Morphogenesis

Cited by 614 publications

References 42 publications

Cellular functions of TC10, a Rho family GTPase: regulation of morphology, signal transduction and cell growth

Cellular functions of TC10, a Rho family GTPase: regulation of morphology, signal transduction and cell growth

Stable and Dynamic Axes of Polarity Use Distinct Formin Isoforms in Budding Yeast

Afr1p has a role in regulating the localization of Mpk1p at the shmoo tip in Saccharomyces cerevisiae

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