20,410 research outputs found
The phosphoinositide-associated protein Rush hour regulates endosomal trafficking in<i>Drosophila</i>
No full textEndocytosis regulates multiple cellular processes, including the protein composition of the plasma membrane, intercellular signaling, and cell polarity. We have identified the highly conserved protein Rush hour (Rush) and show that it participates in the regulation of endocytosis. Rush localizes to endosomes via direct binding of its FYVE (Fab1p, YOTB, Vac1p, EEA1) domain to phosphatidylinositol 3-phosphate. Rush also directly binds to Rab GDP dissociation inhibitor (Gdi), which is involved in the activation of Rab proteins. Homozygous rush mutant flies are viable but show genetic interactions with mutations in Gdi, Rab5, hrs, and carnation, the fly homologue of Vps33. Overexpression of Rush disrupts progression of endocytosed cargo and increases late endosome size. Lysosomal marker staining is decreased in Rush-overexpressing cells, pointing to a defect in the transition between late endosomes and lysosomes. Rush also causes formation of endosome clusters, possibly by affecting fusion of endosomes via an interaction with the class C Vps/homotypic fusion and vacuole protein-sorting (HOPS) complex. These results indicate that Rush controls trafficking from early to late endosomes and from late endosomes to lysosomes by modulating the activity of Rab proteins.</jats:p
PP2A Antagonizes Phosphorylation of Bazooka by PAR-1 to Control Apical-Basal Polarity in Dividing Embryonic Neuroblasts
No full textSummaryBazooka/Par-3 (Baz) is a key regulator of cell polarity in epithelial cells and neuroblasts (NBs). Phosphorylation of Baz by PAR-1 and aPKC is required for its function in epithelia, but little is known about the dephosphorylation mechanisms that antagonize the activities of these kinases or about the relevance of Baz phosphorylation for NB polarity. We found that protein phosphatase 2A (PP2A) binds to Baz via its structural A subunit. By using phospho-specific antibodies, we show that PP2A dephosphorylates Baz at the conserved serine residue 1085 and thereby antagonizes the kinase activity of PAR-1. Loss of PP2A function leads to complete reversal of polarity in NBs, giving rise to an “upside-down” polarity phenotype. Overexpression of PAR-1 or Baz, or mutation of 14-3-3 proteins that bind phosphorylated Baz, causes essentially the same phenotype, indicating that the balance of PAR-1 and PP2A effects on Baz phosphorylation determines NB polarity
ADAM SMITH'S OPTIMISTIC TELEOLOGICAL VIEW OF HISTORY
Get PDFAdam Smith's four-stage theory provides the framework for his writings on history. The fourth stage is the commercial epoch; the culmination of history in this stage is a key component in the conventional interpretation of Adam Smith as a prophet of commercialism. In two historical case studies Smith shows the capacity of commercial society to regenerate itself. This potent capacity suggests that commercial society is inevitable. At a certain point in time it also overcomes the major obstacles to its permanence. Smith's philosophy of history anticipates the end of history views of Kant and Hegel.Political Economy,
protein related to vertebrate HURP, is required for the attachment of centrosomes to the mitotic spindle during syncytial nuclear divisions
No full textThe formation of the mitotic spindle is controlled by the microtubule organizing activity of the centrosomes and by the effects of chromatin-associated Ran-GTP on the activities of spindle assembly factors. In this study we show that Mars, a Drosophila protein with sequence similarity to vertebrate hepatoma upregulated protein (HURP), is required for the attachment of the centrosome to the mitotic spindle. More than 80% of embryos derived from mars mutant females do not develop properly due to severe mitotic defects during the rapid nuclear divisions in early embryogenesis. Centrosomes frequently detach from spindles and from the nuclear envelope and nucleate astral microtubules in ectopic positions. Consistent with its function in spindle organization, Mars localizes to nuclei in interphase and associates with the mitotic spindle, in particular with the spindle poles, during mitosis. We propose that Mars is an important linker between the spindle and the centrosomes that is required for proper spindle organization during the rapid mitotic cycles in early embryogenesis.Deutsche Forschungsgemeinschaft [SFB 590, TP A2, WO 584/4-1, 42
How Might Adam Smith Pay Professors Today?
Get PDFAdam Smith’s proposal for paying professors was intended to induce increased faculty knowledge. If students have imperfect information about what they learn, and universities can only imperfectly measure the input of faculty time in student learning, publications may be used to measure faculty knowledge. If professors’ ability to publish is positively related to their ability to produce student learning, which universities can imperfectly measure, publications may be necessary to attract more able professors. Since research signals faculty knowledge, schools that do not value publications per se could require higher publication standards and pay higher wages than schools that value only publications.
Windei, the Drosophila homolog of mAM/MCAF1, is an essential cofactor of the H3K9 methyl transferase dSETDB1/Eggless in germ line development.
No full textThe epigenetic regulation of gene expression by the covalent modification of histones is a fundamental mechanism required for the proper differentiation of germ line cells during development. Trimethylation of histone 3 lysine 9 (H3K9me3) leads to chromatin silencing and the formation of heterochromatin by recruitment of heterochromatin protein 1 (HP1). dSETDB1/Eggless (Egg), the ortholog of the human methyltransferase SETDB1, is the only essential H3K9 methyltransferase in Drosophila and is required for H3K9 trimethylation in the female germ line. Here we show that Windei (Wde), the Drosophila homolog of mouse mAM and human MCAF1, is an essential cofactor of Egg required for its nuclear localization and function in female germ line cells. By deletion analysis combined with coimmunoprecipitation, we have identified the protein regions in Wde and Egg that are necessary and sufficient for the interaction between the two proteins. We furthermore identified a region of Egg that gets covalently modified by SUMOylation, which may facilitate the formation of higher order chromatin-modifying complexes. Together with Egg, Wde localizes to euchromatin, is enriched on chromosome 4, and binds to the Painting of fourth (POF) protein. Our data provide the first genetic and phenotypic analysis of a mAM/MCAF1 homolog in a model organism and demonstrate its essential function in the survival of germ line cells
ADAM SMITH'S VIEW OF HISTORY: CONSISTENT OR PARADOXICAL?
Get PDFThe conventional interpretation of Adam Smith is that he is a prophet of commercialism. The liberal capitalist reading of Smith is consistent with the view that history culminates in commercial society. The first part of the article develops this optimistic interpretation of Smith's view of history. Smith implies that commercial society is the end of history because 1) it supplies the ends of nature that he identifies; 2) it is inevitable; and 3) it is permanent. The second part of the article shows that Smith has some dark moments in his writings where he seems to reject completely such teleological notions. In this more civic humanist mood he confesses that commercial society does not supply the ends of nature, nor is it inevitable, nor is it permanent. Both views exist in Smith and the commentator is forced to choose between passages in Smith's work in order to support a particular interpretation of the former's view of history.Political Economy,
Adam Smith and Roman Servitudes
Get PDFThis essay is a preprint of an article that appeared at: Tijdschrift voor Rechstsgeschiedenis, 72 (2004), 327–57.This essay discusses Adam Smith historical jurisprudence and his use of Roman law materials in his Lectures on Jurisprudence. It argues that Smith found it difficult to maintain his theory of legal development in the face of a highly developed body of Roman law literature
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