The degradation of some proto-oncogene and lymphokine mRNAs is controlled in part by an AU-rich element (ARE) the 3' untranslated region. It was shown previously (G. Brewer, Mol. Cell. Biol. 11:2460-2466, 1991) that two polypeptides (37 40 kDa) copurified with fractions a 130,000 x g postribosomal supernatant (S130) from K562 cells selectively accelerated c-myc mRNA cell-free decay system. These bound specifically to granulocyte-macrophage colony-stimulating factor UTRs, suggesting they are...

The degradation of some proto-oncogene and lymphokine mRNAs is controlled in part by an AU-rich element (ARE) the 3' untranslated region. It was shown previously (G. Brewer, Mol. Cell. Biol. 11:2460-2466, 1991) that two polypeptides (37 40 kDa) copurified with fractions a 130,000 x g postribosomal supernatant (S130) from K562 cells selectively accelerated c-myc mRNA cell-free decay system. These bound specifically to granulocyte-macrophage colony-stimulating factor UTRs, suggesting they are...

Many intracellular pathogens subvert host membrane trafficking pathways to promote their replication. Toxoplasma multiplies in a membrane-bound parasitophorous vacuole (PV) that interacts with mammalian organelles and intercepts Golgi Rab vesicles acquire sphingolipids. The mechanisms of vesicle internalization processing within the PV remain undefined. We demonstrate sequesters broad range into PV. Correlative light electron microscopy analysis infected cells illustrates intravacuolar Rab1A...

The protozoan parasite Toxoplasma gondii develops within a parasitophorous vacuole (PV) in mammalian cells, where it scavenges cholesterol. When cholesterol is present excess its environment, the expulses this lipid into PV or esterifies for storage bodies. Here, we characterized unique T. homologue of lecithin:cholesterol acyltransferase (LCAT), key enzyme that produces cholesteryl esters via transfer acyl groups from phospholipids to 3-OH free cholesterol, leading removal tissues. TgLCAT...

Human osteoblasts (HOBs) support the growth of human haematopoietic progenitor cells, and survival limited expansion long‐term culture‐initiating cells. Using CD34 + cells murine myelomonocytic cell line NFS‐60 as targets, we previously found that one component HOB‐derived activity is cell‐associated granulocyte colony‐stimulating factor (G‐CSF). However, antibody failed to neutralize all activity, suggesting more than supports In present investigations, asked whether HOB‐derived, non‐G‐CSF...

J M Gott, A Zeeh, D Bell-Pedersen, K Ehrenman, Belfort, and Shub Department of Biological Sciences, State University New York, Albany 12222.

The relationship between mitochondrial genotype and clinical phenotype is complicated in most instances by the heteroplasmic nature of pathogenic mutations. We have previously shown that maternally inherited hearing loss a large Arab-Israeli kindred due to homoplasmic A1555G mutation 12S ribosomal RNA gene [Prezant et al., 1993: Nat Genet 4:289–294]. Family members with this phenotypes ranging from profound completely normal hearing, we there genetic biochemical evidence for nuclear...

Plasmodium parasites successfully colonize different habitats within mammals and mosquitoes, adaptation to various environments is accompanied by changes in their organelle composition size. Previously, we observed that during hepatocyte infection, discards organelles involved invasion expands those implicated biosynthetic pathways. We hypothesized this process regulated autophagy. spp. possess a rudimentary set of known autophagy-related proteins includes the ortholog yeast Atg8. In study,...

Cryptosporidium spp. are responsible for devastating diarrhoea in immunodeficient individuals. In the intestinal tract, developmental stages of parasite confined to apical surfaces epithelial cells. Upon invasion, incorporates microvillous membrane enterocyte form parasitophorous vacuole (PV) and sequesters itself from host cytoplasm by rearranging cytoskeleton. parvum has minimal anabolic capabilities relies on transporters salvage pathways meet its basic metabolic requirements. The...

ABSTRACT Plasmodium parasites undergo continuous cellular renovation to adapt various environments in the vertebrate host and insect vector. In hepatocytes, berghei discards unneeded organelles for replication, such as micronemes involved invasion. Concomitantly, intrahepatic expand apicoplast that produce essential metabolites. We previously showed ATG8 conjugation system is upregulated P. liver forms (PbATG8) localizes membranes of cytoplasmic vesicles. Here, we focus on contribution...

Several features of the split td gene phage T4 suggest an RNA processing mechanism analogous to that self-splicing rRNA Tetrahymena and other group I eukaryotic introns. Previous work has revealed conserved sequence elements ability td-encoded self-splice in vitro. We show here a noncoded guanosine residue is covalently joined 5' end intron during processing. Further, we demonstrate existence linear circular forms extracted from T4-infected cells uninfected Escherichia coli expressing cloned...

Several proteins that play key roles in cholesterol synthesis, regulation, trafficking and signaling are united by sharing the phylogenetically conserved 'sterol-sensing domain' (SSD). The intracellular parasite Toxoplasma possesses at least one gene coding for a protein containing canonical SSD. We investigated role of this to provide information on lipid regulatory mechanisms parasite. sequence predicts an uncharacterized Niemann-Pick, type C1-related (NPC1) with significant identity human...

Toxoplasma is a protozoan parasite proficiently adapted to thrive in parasitophorous vacuole (PV) formed the cytoplasm of large variety mammalian cells. As an actively dividing organism, must adjust lipid composition its membranes preserve organelle vitality and expand size PV membrane accommodate growing progeny. We showed that takes up host lipids can expel major ATP-dependent process. In order provide detailed mechanistic insights into trafficking phenomena relevant biology, we...

The prokaryote Chlamydia trachomatis and the protozoan Toxoplasma gondii, two obligate intracellular pathogens of humans, have evolved a similar modus operandi to colonize their host cell salvage nutrients from organelles. In order gain fundamental knowledge on pathogenicity these microorganisms, we established culture model whereby single fibroblasts are coinfected by C. T. gondii. We previously reported that compete for same nutrient pools in cells holds significant competitive advantage...

In Dictyostelium discoideum counting factor (CF), a secreted ∼450-kDa complex of polypeptides, inhibits group and fruiting body size. When the gene encoding countin (a component CF) was disrupted, cells formed large groups. We find that recombinant causes developing to form small groups, with an EC50 ∼3 ng/ml, affects cAMP signal transduction in same manner as semipurified CF. Recombinant increases cell motility, decreases cell-cell adhesion, regulates expression similar effect However, does...

A secreted 450-kDa complex of proteins called counting factor (CF) is part a negative feedback loop that regulates the size groups formed by developing Dictyostelium cells. Two components CF are countin and CF50. Both recombinant CF50 decrease group in Dictyostelium. countin- cells have decreased cAMP-stimulated cAMP pulse, whereas potentiates pulse. We find cf50- an increased decreases suggesting opposite effects on signal transduction. In addition, Erk2 activation. However, like countin,...

Developing Dictyostelium cells form structures containing ∼20,000 cells. The size regulation mechanism involves a secreted counting factor (CF) repressing cytosolic glucose levels. Glucose or metabolite affects cell-cell adhesion and motility; these in turn affect whether group stays together, loses cells, even breaks up. NADPH-coupled aldehyde reductase reduces wide variety of aldehydes to the corresponding alcohols, including converting sorbitol. levels this enzyme previously appeared be...

Toxoplasma and Chlamydia trachomatis are obligate intracellular pathogens that have evolved analogous strategies to replicate within mammalian cells. Both known extensively remodel the cytoskeleton, recruit endocytic exocytic organelles their respective vacuoles. However, how important these activities for infectivity by either pathogen remains elusive. Here, we developed a novel co-infection system gain insights into developmental cycles of C. infecting human cells with both pathogens,...