Department of Pharmacology and Cancer Biology, Duke University Medical Centre, Durham, NC 27710, USA
* Author for correspondence (e-mail: daniel.lew{at}duke.edu)
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Introduction |
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Polarized structures |
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Polarization during the cell cycle |
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Components of the polarized patch |
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Bud site selection
The location of the polarized patch is not random within the cell. Newborn cells carry spatial landmarks (including Bud8p at the distal tip) that influence the location of the polarized patch in the subsequent cell cycle. The Rsr1p GTPase and its guanine nucleotide exchange factor (GEF) Bud5p and GTPase-activating protein (GAP) Bud2p are required for proper localization of the polarized patch to the site specified by the spatial landmarks, and in their absence the polarized patch forms at a random location.
Polarity establishment
The Rho-family GTPase Cdc42p and its GEF Cdc24p are essential for assembly of the polarized patch and septin ring, and for the polarization of actin cables and cortical actin patches. As such, they are considered the master regulators of polarity establishment in yeast. Genetic studies indicate that the Cdc42p effectors Cla4p, Ste20p, Gic1p and Gic2p, as well as the scaffold proteins Bem1p, Boi1p and Boi2p act together with Cdc42p and Cdc24p to establish polarity.
Rho-GAPs
At least four GAPs can stimulate GTP hydrolysis by Cdc42p. Phenotypic analysis suggests that Bem2p is important for polarity establishment, although it also has links to Rho1p and the control of cell wall integrity and MAPK signaling. By contrast, Rga1p, Rga2p and Bem3p have been implicated in promoting the assembly of the septin ring around the polarized patch.
Polarisome
The polarisome is a protein complex thought to form a link between polarity establishment factors and actin cables. The formin Bni1p promotes nucleation and growth of actin cables, and Spa2p and Bud6p are important for Bni1p localization and function. Although actin polarization is essential for bud growth, the polarisome components are not essential, perhaps because another formin, Bnr1p, is recruited to the septin ring and can nucleate polarized actin cables from there.
Polarized secretion
The type V myosin Myo2p, with associated light chains Mlc1p and Cmd1p (calmodulin), transports secretory vesicles containing the Rab-family GTPase Sec4p to the polarized patch. The SNARE-binding protein Sec1p is also polarized and essential for vesicle fusion with the plasma membrane. Myo2p also transports organelles and microtubules along actin cables, while the related Myo4p transports mRNA-protein complexes, generating mother-bud differences in protein translation.
Exocyst
The exocyst is a multiprotein complex that tethers secretory vesicles to the plasma membrane prior to fusion.
Cell wall
Glucan polymers make up a large portion of the cell wall, and the glucan synthases Fks1p and Gcs2p extrude the polymers across the plasma membrane at sites of cell growth. A cell wall protein (Cwh43p) and a putative sensor of cell wall stress (Slg1p) are also polarized, as is the Rho1p GEF Rom2p. Rho1p is a multifunctional GTPase that activates glucan synthase as well as the protein kinase C Pkc1p.
MAPK signaling
Cell wall stress activates the `cell integrity' MAPK signaling cascade, several members of which are found in the polarized patch (Rho1p, Pkc1p, Mkk1p, Mkk2p and the MAPK Slt2p). This pathway activates transcription of cell-wall-related genes and contributes to halting of the cell cycle under conditions of stress, through the morphogenesis checkpoint.
RAM
A recently identified signaling pathway termed the RAM (regulation of Ace2p activity and cellular morphogenesis) contains interacting components required for optimal polarization as well as asymmetric mother/daughter gene expression. During bud growth these proteins are localized to the polarized patch, but some components relocate to the daughter cell nucleus in the bud following mitosis.
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A hierarchical model for cell polarization |
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References |
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