A Gip1p–Glc7p phosphatase complex regulates septin organization and spore wall formation

Sporulation of Saccharomyces cerevisiae is a developmental process in which a single cell is converted into four haploid spores. GIP1, encoding a developmentally regulated protein phosphatase 1 interacting protein, is required for spore formation. Here we show that GIP1 and the protein phosphatase 1 encoded by GLC7 play essential roles in spore development. The gip1Δ mutant undergoes meiosis and prospore membrane formation normally, but is specifically defective in spore wall synthesis. We demonstrate that in wild-type cells, distinct layers of the spore wall are deposited in a specific temporal order, and that gip1Δ cells display a discrete arrest at the onset of spore wall deposition. Localization studies revealed that Gip1p and Glc7p colocalize with the septins in structures underlying the growing prospore membranes. Interestingly, in the gip1Δ mutant, not only is Glc7p localization altered, but septins are also delocalized. Similar phenotypes were observed in a glc7–136 mutant, which expresses a Glc7p defective in interacting with Gip1p. These results indicate that a Gip1p–Glc7p phosphatase complex is required for proper septin organization and initiation of spore wall formation during sporulation

Modelling Transmission of Vector-Borne Pathogens Shows Complex Dynamics When Vector Feeding Sites Are Limited

The relationship between species richness and the prevalence of vector-borne disease has been widely studied with a range of outcomes. Increasing the number of host species for a pathogen may decrease infection prevalence (dilution effect), increase it (amplification), or have no effect. We derive a general model, and a specific implementation, which show that when the number of vector feeding sites on each host is limiting, the effects on pathogen dynamics of host population size are more complex than previously thought. The model examines vector-borne disease in the presence of different host species that are either competent or incompetent (i.e. that cannot transmit the pathogen to vectors) as reservoirs for the pathogen. With a single host species present, the basic reproduction ratio R0 is a non-monotonic function of the population size of host individuals (H), i.e. a value exists that maximises R0. Surprisingly, if a reduction in host population size may actually increase R0. Extending this model to a two-host species system, incompetent individuals from the second host species can alter the value of which may reverse the effect on pathogen prevalence of host population reduction. We argue that when vector-feeding sites on hosts are limiting, the net effect of increasing host diversity might not be correctly predicted using simple frequency-dependent epidemiological models

Novel suppressors of α-synuclein toxicity identified using yeast

The mechanism by which the Parkinson’s disease-related protein α-synuclein (α-syn) causes neurodegeneration has not been elucidated. To determine the genes that protect cells from α-syn, we used a genetic screen to identify suppressors of the super sensitivity of the yeast Saccharomyces cerevisiae expressing α-syn to killing by hydrogen peroxide. Forty genes in ubiquitin-dependent protein catabolism, protein biosynthesis, vesicle trafficking and the response to stress were identified. Five of the forty genes—ENT3, IDP3, JEM1, ARG2 and HSP82—ranked highest in their ability to block α-syn-induced reactive oxygen species accumulation, and these five genes were characterized in more detail. The deletion of any of these five genes enhanced the toxicity of α-syn as judged by growth defects compared with wild-type cells expressing α-syn, which indicates that these genes protect cells from α-syn. Strikingly, four of the five genes are specific for α-syn in that they fail to protect cells from the toxicity of the two inherited mutants A30P or A53T. This finding suggests that α-syn causes toxicity to cells through a different pathway than these two inherited mutants. Lastly, overexpression of Ent3p, which is a clathrin adapter protein involved in protein transport between the Golgi and the vacuole, causes α-syn to redistribute from the plasma membrane into cytoplasmic vesicular structures. Our interpretation is that Ent3p mediates the transport of α-syn to the vacuole for proteolytic degradation. A similar clathrin adaptor protein, epsinR, exists in humans