An acidic loop in the forkhead-associated domain of the yeast meiosis-specific kinase Mek1 interacts with a specific motif in a subset of Mek1 substrates.

The meiosis-specific kinase Mek1 regulates key steps in meiotic recombination in the budding yeast, Saccharomyces cerevisiae. MEK1 limits resection at double-strand break (DSB) ends and is required for preferential strand invasion into homologs, a process known as interhomolog bias. After strand invasion, MEK1 promotes phosphorylation of the synaptonemal complex protein Zip1 that is necessary for DSB repair mediated by a crossover-specific pathway that enables chromosome synapsis.

Membrane and organelle rearrangement during ascospore formation in budding yeast.

SUMMARYIn ascomycete fungi, sexual spores, termed ascospores, are formed after meiosis. Ascospore formation is an unusual cell division in which daughter cells are created within the cytoplasm of the mother cell by generation of membranes that encapsulate each of the haploid chromosome sets created by meiosis. This review describes the molecular events underlying the creation, expansion, and closure of these membranes in the budding yeast, .

An acidic loop in the FHA domain of the yeast meiosis-specific kinase Mek1 interacts with a specific motif in a subset of Mek1 substrates.

The meiosis-specific kinase Mek1 regulates key steps in meiotic recombination in the budding yeast, limits resection at the double strand break (DSB) ends and is required for preferential strand invasion into homologs, a process known as interhomolog bias. After strand invasion, promotes phosphorylation of the synaptonemal complex protein Zip1 that is necessary for DSB repair mediated by a crossover specific pathway that enables chromosome synapsis. In addition, Mek1 phosphorylation of the meiosis-specific transcription factor, Ndt80, regulates the meiotic recombination checkpoint that prevents exit from pachytene when DSBs are present.

Pharmacological interventions for lipid transport disorders.

The recent discovery that defects in inter-organelle lipid transport are at the heart of several neurological and neurodegenerative disorders raises the challenge of identifying therapeutic strategies to correct lipid transport defects. This perspective highlights two potential strategies suggested by the study of lipid transport in budding yeast. In the first approach, small molecules are proposed that enhance the lipid transfer activity of proteins and thereby compensate for reduced transport.

Recruitment of the lipid kinase Mss4 to the meiotic spindle pole promotes prospore membrane formation in .

Spore formation in the budding yeast, , involves de novo creation of four prospore membranes, each of which surrounds a haploid nucleus resulting from meiosis. The meiotic outer plaque (MOP) is a meiosis-specific protein complex associated with each meiosis II spindle pole body (SPB). Vesicle fusion on the MOP surface creates an initial prospore membrane anchored to the SPB.

Interaction between VPS13A and the XK scramblase is important for VPS13A function in humans.

VPS13 family proteins form conduits between the membranes of different organelles through which lipids are transferred. In humans, there are four VPS13 paralogs, and mutations in the genes encoding each of them are associated with different inherited disorders. VPS13 proteins contain multiple conserved domains.

Special Issue: Formation and Function of Fungal Ascospores.

I wish to thank all of the authors who contributed papers to this Special Issue on the Formation and Function of Ascospores [...

Suppression of Vps13 adaptor protein mutants reveals a central role for PI4P in regulating prospore membrane extension.

Vps13 family proteins are proposed to function in bulk lipid transfer between membranes, but little is known about their regulation. During sporulation of Saccharomyces cerevisiae, Vps13 localizes to the prospore membrane (PSM) via the Spo71-Spo73 adaptor complex. We previously reported that loss of any of these proteins causes PSM extension and subsequent sporulation defects, yet their precise function remains unclear.

Genetic Dissection of Vps13 Regulation in Yeast Using Disease Mutations from Human Orthologs.

The VPS13 family of proteins have emerged as key players in intracellular lipid transport and human health. Humans have four different orthologs, the dysfunction of which leads to different diseases. Yeast has a single gene, which encodes a protein that localizes to multiple different membrane contact sites.

A Conserved Machinery Underlies the Synthesis of a Chitosan Layer in the Chlamydospore Cell Wall.

The polysaccharide chitosan is found in the cell wall of specific cell types in a variety of fungal species where it contributes to stress resistance, or in pathogenic fungi, virulence. Under certain growth conditions, the pathogenic yeast forms a cell type termed a chlamydospore, which has an additional internal layer in its cell wall compared to hyphal or yeast cell types. We report that this internal layer of the chlamydospore wall is rich in chitosan.

Unconventional Constituents and Shared Molecular Architecture of the Melanized Cell Wall of and Spore Wall of .

The fungal cell wall serves as the interface between the cell and the environment. Fungal cell walls are composed largely of polysaccharides, primarily glucans and chitin, though in many fungi stress-resistant cell types elaborate additional cell wall structures. Here, we use solid-state nuclear magnetic resonance spectroscopy to compare the architecture of cell wall fractions isolated from spores and melanized cells.

XK is a partner for VPS13A: a molecular link between Chorea-Acanthocytosis and McLeod Syndrome.

Vps13 is a highly conserved lipid transfer protein found at multiple interorganelle membrane contact sites where it mediates distinct processes. In yeast, recruitment of Vps13 to different contact sites occurs via various partner proteins. In humans, four VPS13 family members, A-D, are associated with different diseases.

A Noncanonical Hippo Pathway Regulates Spindle Disassembly and Cytokinesis During Meiosis in .

Meiosis in the budding yeast is used to create haploid yeast spores from a diploid mother cell. During meiosis II, cytokinesis occurs by closure of the prospore membrane, a membrane that initiates at the spindle pole body and grows to surround each of the haploid meiotic products. Timely prospore membrane closure requires , which encodes an STE20 family GCKIII kinase.

Fungal Pathogens: Shape-Shifting Invaders.

Fungal infections are on the rise due to new medical procedures that have increased the number of immune compromised patients, antibacterial antibiotics that disrupt the microbiome, and increased use of indwelling medical devices that provide sites for biofilm formation. Key to understanding the mechanisms of pathogenesis is to determine how fungal morphology impacts virulence strategies. For example, small budding cells use very different strategies to disseminate compared with long hyphal filaments.

A Novel Assay Reveals a Maturation Process during Ascospore Wall Formation.

The ascospore wall of the budding yeast consists of inner layers of similar composition to the vegetative cell wall and outer layers made of spore-specific components that confer increased stress resistance on the spore. The primary constituents of the outer spore wall are chitosan, dityrosine, and a third component termed Chi that has been identified by spectrometry but whose chemical structure is not known. The lipophilic dye monodansylpentane readily stains lipid droplets inside of newly formed ascospores but, over the course of several days, the spores become impermeable to the dye.

Developmentally regulated internal transcription initiation during meiosis in budding yeast.

Sporulation of budding yeast is a developmental process in which cells undergo meiosis to generate stress-resistant progeny. The dynamic nature of the budding yeast meiotic transcriptome has been well established by a number of genome-wide studies. Here we develop an analysis pipeline to systematically identify novel transcription start sites that reside internal to a gene.

The meiosis-specific Cdc20 family-member Ama1 promotes binding of the Ssp2 activator to the Smk1 MAP kinase.

Smk1 is a meiosis-specific MAP kinase (MAPK) in budding yeast that is required for spore formation. It is localized to prospore membranes (PSMs), the structures that engulf haploid cells during meiosis II (MII). Similar to canonically activated MAPKs, Smk1 is controlled by phosphorylation of its activation-loop threonine (T) and tyrosine (Y).

Dynamic localization of a yeast development-specific PP1 complex during prospore membrane formation is dependent on multiple localization signals and complex formation.

During the developmental process of sporulation in , membrane structures called prospore membranes are formed de novo, expand, extend, acquire a round shape, and finally become plasma membranes of the spores. encodes a regulatory/targeting subunit of protein phosphatase type 1 that is required for sporulation. Gip1 recruits the catalytic subunit Glc7 to septin structures that form along the prospore membrane; however, the molecular basis of its localization and function is not fully understood.

Long-Chain Polyprenols Promote Spore Wall Formation in .

Dolichols are isoprenoid lipids of varying length that act as sugar carriers in glycosylation reactions in the endoplasmic reticulum. In , there are two -prenyltransferases that synthesize polyprenol-an essential precursor to dolichol. These enzymes are heterodimers composed of Nus1 and either Rer2 or Srt1.

reconstitution of the yeast spore wall dityrosine layer discloses the mechanism of its assembly.

In response to nutrient starvation, diploid cells of the budding yeast differentiate into a dormant form of haploid cell termed a spore. The dityrosine layer forms the outermost layer of the wall of spores and endows them with resistance to environmental stresses. ll-Bisformyl dityrosine is the main constituent of the dityrosine layer, but the mechanism of its assembly remains elusive.

Eighth International Chorea-Acanthocytosis Symposium: Summary of Workshop Discussion and Action Points.

Chorea-Acanthocytosis (ChAc) is a rare hereditary neurological disorder characterized by abnormal movements, red blood cell pathology, and progressive neurodegeneration. Little is understood of the pathogenesis of ChAc and related disorders (collectively Neuroacanthocytosis). The Eighth International Chorea-Acanthocytosis Symposium was held in May 2016 in Ann Arbor, MI, USA, and focused on molecular mechanisms driving ChAc pathophysiology.

Predicted RNA Binding Proteins Pes4 and Mip6 Regulate mRNA Levels, Translation, and Localization during Sporulation in Budding Yeast.

In response to starvation, diploid cells of undergo meiosis and form haploid spores, a process collectively referred to as sporulation. The differentiation into spores requires extensive changes in gene expression. The transcriptional activator Ndt80 is a central regulator of this process, which controls many genes essential for sporulation.

Congenital valvular defects associated with deleterious mutations in the gene.

Background: The underlying molecular aetiology of congenital heart defects is largely unknown. The aim of this study was to explore the genetic basis of non-syndromic severe congenital valve malformations in two unrelated families.

Methods: Whole-exome analysis was used to identify the mutations in five patients who suffered from severe valvular malformations involving the pulmonic, tricuspid and mitral valves.

Correction: Mek1 Down Regulates Rad51 Activity during Yeast Meiosis by Phosphorylation of Hed1.

[This corrects the article DOI: 10.1371/journal.pgen.