title: Cyclical regulation of the exocyst and cell polarity determinants for polarized cell growth.
abstract: Polarized exocytosis is important for morphogenesis and cell growth. The exocyst is a multiprotein complex implicated in tethering secretory vesicles at specific sites of the plasma membrane for exocytosis. In the budding yeast, the exocyst is localized to sites of bud emergence or the tips of small daughter cells, where it mediates secretion and cell surface expansion. To understand how exocytosis is spatially controlled, we systematically analyzed the localization of Sec15p, a member of the exocyst complex and downstream effector of the rab protein Sec4p, in various mutants. We found that the polarized localization of Sec15p relies on functional upstream membrane traffic, activated rab protein Sec4p, and its guanine exchange factor Sec2p. The initial targeting of both Sec4p and Sec15p to the bud tip depends on polarized actin cable. However, different recycling mechanisms for rab and Sec15p may account for the different kinetics of polarization for these two proteins. We also found that Sec3p and Sec15p, though both members of the exocyst complex, rely on distinctive targeting mechanisms for their localization. The assembly of the exocyst may integrate various cellular signals to ensure that exocytosis is tightly controlled. Key regulators of cell polarity such as Cdc42p are important for the recruitment of the exocyst to the budding site. Conversely, we found that the proper localization of these cell polarity regulators themselves also requires a functional exocytosis pathway. We further report that Bem1p, a protein essential for the recruitment of signaling molecules for the establishment of cell polarity, interacts with the exocyst complex. We propose that a cyclical regulatory network contributes to the establishment and maintenance of polarized cell growth in yeast.
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, PA 19104-6018, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Zajac
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Sun
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
mesh_terms: D000199:Actins / Q000737:chemistry; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000483:Alleles; D019521:Body Patterning; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D019070:Cell Lineage; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D005089:Exocytosis; D019204:GTP-Binding Proteins / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005838:Genotype; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors; D047468:Immunoprecipitation; D007700:Kinetics; D008856:Microscopy, Fluorescence; D008858:Microscopy, Phase-Contrast; D009154:Mutation; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015398:Signal Transduction; D013696:Temperature; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D014335:Tropomyosin / Q000737:chemistry; D033921:Vesicular Transport Proteins; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D019086:Bridged Bicyclo Compounds, Heterocyclic; D020662:Guanine Nucleotide Exchange Factors; C060862:SEC15 protein, S cerevisiae; C064456:SEC2 protein, S cerevisiae; C103130:SEC3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D013844:Thiazoles; D053778:Thiazolidines; D014335:Tropomyosin; D033921:Vesicular Transport Proteins; C073129:BEM1 protein, S cerevisiae; D049452:Green Fluorescent Proteins; D019204:GTP-Binding Proteins; C064320:SEC4 protein, S cerevisiae; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae; D020691:rab GTP-Binding Proteins; C037068:latrunculin B