A yeast t-SNARE involved in endocytosis Séron, K; Tieaho, V; Prescianotto-Baschong, C ...
Molecular biology of the cell,
10/1998, Letnik:
9, Številka:
10
Journal Article
Recenzirano
Odprti dostop
The ORF YOL018c (TLG2) of Saccharomyces cerevisiae encodes a protein that belongs to the syntaxin protein family. The proteins of this family, t-SNAREs, are present on target organelles and are ...thought to participate in the specific interaction between vesicles and acceptor membranes in intracellular membrane trafficking. TLG2 is not an essential gene, and its deletion does not cause defects in the secretory pathway. However, its deletion in cells lacking the vacuolar ATPase subunit Vma2p leads to loss of viability, suggesting that Tlg2p is involved in endocytosis. In tlg2Delta cells, internalization was normal for two endocytic markers, the pheromone alpha-factor and the plasma membrane uracil permease. In contrast, degradation of alpha-factor and uracil permease was delayed in tlg2Delta cells. Internalization of positively charged Nanogold shows that the endocytic pathway is perturbed in the mutant, which accumulates Nanogold in primary endocytic vesicles and shows a greatly reduced complement of early endosomes. These results strongly suggest that Tlg2p is a t-SNARE involved in early endosome biogenesis.
In the budding yeast Saccharomyces cerevisiae, mutations in the essential gene CDC1 cause defects in Golgi inheritance and actin polarization. However, the biochemical function of Cdc1p is unknown. ...Previous work showed that cdc1 mutants accumulate intracellular Ca super(2+) and display enhanced sensitivity to the extracellular Mn super(2+) concentration, suggesting that Cdc1p might regulate divalent cation homeostasis. By contrast, our data indicate that Cdc1p is a Mn super(2+)-dependent protein that can affect Ca super(2+) levels. We identified a cdc1 allele that activates Ca super(2+) signaling but does not show enhanced sensitivity to the Mn super(2+) concentration. Furthermore, our studies show that Cdc1p is an endoplasmic reticulum-localized transmembrane protein with a putative phosphoesterase domain facing the lumen. cdc1 mutant cells accumulate an unidentified phospholipid, suggesting that Cdc1p may be a lipid phosphatase. Previous work showed that deletion of the plasma membrane Ca super(2+) channel Cch1p partially suppressed the cdc1 growth phenotype, and we find that deletion of Cch1p also suppresses the Golgi inheritance and actin polarization phenotypes. The combined data fit a model in which the cdc1 mutant phenotypes result from accumulation of a phosphorylated lipid that activates Ca super(2+) signaling.
Deconstructing Golgi Inheritance Rossanese, Olivia W.; Glick, Benjamin S.
Traffic (Copenhagen, Denmark),
September 2001, Letnik:
2, Številka:
9
Journal Article
Recenzirano
Eukaryotic cells use a variety of strategies to inherit the Golgi apparatus. During vertebrate mitosis, the Golgi reorganizes dramatically in a process that seems to be driven by the reversible ...fragmentation of existing Golgi structures and the temporary redistribution of Golgi components to the endoplasmic reticulum. Several proteins that participate in vertebrate Golgi inheritance have been identified, but their detailed functions remain unknown. A comparison between vertebrates and other eukaryotes reveals common mechanisms of Golgi inheritance. In many cell types, Golgi stacks undergo fission early in mitosis. Some cells exhibit a further Golgi breakdown that is probably due to a mitotic inhibition of membrane traffic. In all eukaryotes examined, Golgi inheritance involves either the partitioning of pre‐existing Golgi elements between the daughter cells or the emergence of new Golgi structures from the endoplasmic reticulum, or some combination of these two pathways.
A potent series of inhibitors against the B-Raf super(V600E kinase have been developed that show excellent activity in cellular assays and good oral bioavailability in rats. The key structural ...features of the series are an arylsulfonamide headgroup, a thiazole core, and a fluorine ortho to the sulfonamide nitrogen.)
A potent series of inhibitors against the B-Raf
V600E kinase have been developed that show excellent activity in cellular assays and good oral bioavailability in rats. The key structural features of ...the series are an arylsulfonamide headgroup, a thiazole core, and a fluorine
ortho to the sulfonamide nitrogen.
Fragmentsuche: Liganden, die an die GTPase K‐Ras binden und die Aktivität des Nukleotidaustauschfaktors Sos verändern, wurden mit einem fragmentbasierten Screening unter Verwendung von ...NMR‐Spektroskopie gefunden. Strukturdaten zeigen, wie die von den Fragmenten abgeleiteten Treffer an den K‐Ras‐Guanosindiphosphat‐Komplex binden (siehe Bild), und liefern einen Ausgangspunkt für die Entwicklung von Wirkstoffen, die K‐Ras‐Aktivierung und ‐Signalisierung beeinflussen.
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