Origins of Cell Polarity

ing proteins assembles at the site marked by the cue, *Department of Molecular and Cell Biology then a polarized actin and septin cytoskeleton assemUniversity of California, Berkeley bles, and the secretory apparatus becomes oriented Berkeley, California 94720 toward the spatial cue. Considerable information about †Department of Molecular and Cellular Physiology bud formation has been obtained during the past several Beckman Center for Molecular and Genetic Medicine years, and some advances in our understanding of matStanford University School of Medicine ing projection formation and orientation have also been Stanford, California 94305-5426 made recently. Bud Site Selection Occurs in Response Cell polarity is the ultimate reflection of complex mechato Intrinsic Spatial Cues nisms that establish and maintain functionally specialBoth genotype and nutritional conditions determine ized domains in the plasma membrane and cytoplasm. which of three budding patterns yeast cells will adopt. The spatial arrangement and protein composition of MATa and MATa cells construct bud sites adjacent to these domains facilitate cellular processes as diverse the previous bud site (axial budding pattern), while as differentiation, localized membrane growth, activaMATa/MATa cells bud from sites that are either near tion of the immune response, directional cell migration, the previous bud site or at the opposite end of the cell and vectorial transport of molecules across cell layers. (bipolar budding pattern) (Chant and Pringle, 1995, and In this review, two phylogenetically distant eukaryotic references therein). A yeast cell undergoing pseudohycells, budding yeast and mammalian epithelial cells, are phal growth always buds from the same pole, namely examined to highlight advances in our understanding the pole opposite the original junction with its mother of how cell polarity is established. Both of these cells cell (unipolar budding pattern) (Kron et al., 1994). These are characterized by a high degree of cellular asymmetry three budding patterns presumably optimize the evolu(see Figure 1) and have been used extensively to study tionary fitnessof yeast growing in the haploid and diploid how cell polarity is developed. The specific focus here states, depending on the supply of nutrients (Gimeno is on the molecular nature of the intrinsic and extrinsic and Fink, 1992). Placement of cortical cues for each spatial cues that establish structural and molecular budding pattern is dependent upon one of two cytoskelasymmetry at the cell surface, the mechanisms that inetal proteins, septins and actin. terpret signals from these cues to generate new memPartial loss-of-function mutations inseptins, cytoskelbrane domains, and the reorganization of thecell around etal proteins that are arranged in a ring at the bud neck these spatially defined sites (see Figure 2). The evidence and are required for cytokinesis (Sanders and Field, supports a model in which a hierarchy of three sequen1994), can cause defects in the axial budding of a or a tial stages is required to establish cell polarity from a cells (Flescher et al., 1993). This result suggests that spatial cue (see Figure 3). This hierarchy consists of the septins assembled during the previous cell cycle are a following: marking a site and decoding the cue; reinforccomponent of the spatial cue for selection of an axial ing the cue; propagating the cue. Feedback regulation bud site during one cell cycle. Two novel proteins reat each stage coordinates and reinforces the proper quired for axial budding, Bud3 and Bud4, colocalize with ordering of these events, resulting in the maintenance the septins, but are lost from the bud neck in septin of cell polarity. Each level of this hierarchy is color coded mutants (Chant et al., 1995; Herskowitz et al., 1995). in the figures to facilitate comparisons between yeast These observations support the view that septins are