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Saccharomyces cerevisiae K1 killer strains are infected by the M1 double-stranded RNA virus encoding a secreted protein toxin that kills sensitive cells by disrupting cytoplasmic membrane function. Toxin binding to spheroplasts is mediated by Kre1p, a cell wall protein initially attached to the plasma membrane by its C-terminal GPI anchor. Kre1p binds toxin directly. Both cells and spheroplasts of...
E2 enzymes catalyze attachment of ubiquitin and ubiquitin-like proteins to lysine residues directly or through E3-mediated reactions. The small ubiquitin-like modifier SUMO regulates nuclear transport, stress response, and signal transduction in eukaryotes and is essential for cell-cycle progression in yeast. In contrast to most ubiquitin conjugation, the SUMO E2 enzyme Ubc9 is sufficient for substrate...
Chili peppers produce the pungent vanilloid compound capsaicin, which offers protection from predatory mammals. Birds are indifferent to the pain-producing effects of capsaicin and therefore serve as vectors for seed dispersal. Here, we determine the molecular basis for this species-specific behavioral response by identifying a domain of the rat vanilloid receptor that confers sensitivity to capsaicin...
Pain transmission in the spinal cord is regulated by a balance of facilitatory and inhibitory influences operating on the neural circuits of the somatosensory system. The transcriptional repressor DREAM acts constitutively to suppress prodynorphin expression in spinal cord neurons. Knocking out DREAM results in sufficient dynorphin expression to produce a strong reduction in generalized pain behavior,...
How sister kinetochores attach to microtubules from opposite spindle poles during mitosis (bi-orientation) remains poorly understood. In yeast, the ortholog of the Aurora B-INCENP protein kinase complex (Ipl1-Sli15) may have a role in this crucial process, because it is necessary to prevent attachment of sister kinetochores to microtubules from the same spindle pole. We investigated IPL1 function...
Human herpesvirus-8 (HHV-8) is implicated in the pathogenesis of Kaposi's sarcoma. HHV-8 envelope glycoprotein B possesses the RGD motif known to interact with integrin molecules, and HHV-8 infectivity was inhibited by RGD peptides, antibodies against RGD-dependent α3 and β1 integrins, and by soluble α3β1 integrin. Expression of human α3 integrin increased the infectivity of virus for Chinese hamster...
Three membrane microdomains can be identified on docked vacuoles: ''outside'' membrane, not in contact with other vacuoles, ''boundary'' membrane that contacts adjacent vacuoles, and ''vertices,'' where boundary and outside membrane meet. In living cells and in vitro, vacuole fusion occurs at vertices rather than from a central pore expanding radially. Vertex fusion leaves boundary membrane within...
Myosin-1c (also known as myosin-Iβ) has been proposed to mediate the slow component of adaptation by hair cells, the sensory cells of the inner ear. To test this hypothesis, we mutated tyrosine-61 of myosin-1c to glycine, conferring susceptibility to inhibition by N 6 -modified ADP analogs. We expressed the mutant myosin-1c in utricular hair cells of transgenic mice, delivered an ADP analog...
Alternative splicing of the gene for Stat3, a transcription factor activated by the IL-6 family of cytokines, produces two isoforms: Stat3α and a dominant-negative variant, Stat3β. Stat3β-deficient mice were generated by gene targeting. Despite intact expression and phosphorylation of Stat3α, overall Stat3 activity was impaired in Stat3β -/- cells. Global comparison of transcription...
The diverse consequences of different viral infections on the human population reflect both the history of their origins and the nature of their ongoing evolution. Advances in the ease of finding and characterizing viral genome sequences are having a major impact on our understanding of the diversity of human viruses and of their relatives infecting other species.
When many cells divide, the nuclear envelope poses a problem: the spindle microtubules can't access the chromosomes. Two recent papers in Cell describe how the spindle solves this problem by literally pulling open the nucleus at the beginning of mitosis.
TALL-1/BAFF/BLyS was recently identified as a member of the tumor necrosis factor (TNF) ligand family. The crystal structure of the functional soluble TALL-1 (sTALL-1) has been determined at 3.0 Å. sTALL-1 forms a virus-like assembly with 200 Å diameter in the crystals, containing 60 sTALL-1 monomers. The cluster formation is mediated by a ''flap'' region of the sTALL-1 monomer. The virus-like assembly...
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