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The article presents a study that explores structures of neurokinin 1 receptor in complex with Gq and Gs proteins reveal substance P binding mode and unique activation features. It mentions that structures provide important structural insights into ligand and G protein promiscuity, the lack of basal signaling, and agonist- and antagonist-induced conformations in the neurokinin receptor family.

The unfolded protein response (UPR), which is activated when unfolded or misfolded proteins accumulate in the endoplasmic reticulum, has been implicated in the normal physiology of immune defense and in several human diseases, including diabetes, cancer, neurodegenerative disease, and inflammatory disease. In this study, we found that the nervous system controlled the activity of a noncanonical UPR pathway required for innate immunity in Caenorhabditis elegans. OCTR-1, a putative octopamine G protein-coupled catecholamine receptor (GPCR, G protein-coupled receptor), functioned in sensory neurons designated ASH and ASI to actively suppress innate immune responses by down-regulating the expression of noncanonical UPR genes pqn/abu in nonneuronal tissues. Our findings suggest a molecular mechanism by which the nervous system may sense inflammatory responses and respond by controlling stress-response pathways at the organismal level. [ABSTRACT FROM AUTHOR]

Chromosomal rearrangements that create gene fusions are common features of human tumors. The prevailing view is that the resultant chimeric transcripts and proteins are abnormal, tumor-specific products that provide tumor cells with a growth and/or survival advantage. We show that normal endometrial stromal cells contain a specific chimeric RNA joining 5′ exons of the JAZF1 gene on chromosome 7p15 to 3′ exons of the Polycomb group gene JJAZ1/SUZ12 on chromosome 17q11 and that this RNA is translated into JAZF1-JJAZ1, a protein with anti-apoptotic activity. The JAZF1-JJAZ1 RNA appears to arise from physiologically regulated trans-splicing between precursor messenger RNAs for JAZF1 and JJAZ1. The chimeric RNA and protein are identical to those produced from a gene fusion found in human endometrial stromal tumors. These observations suggest that certain gene fusions may be pro-neoplastic owing to constitutive expression of chimeric gehe products normally generated by trans-splicing of RNAs in developing tissues. [ABSTRACT FROM AUTHOR]

Activation of cyclin-dependent kinase 1 (Cdk1) has been linked to cell death of postmitotic neurons in brain development and disease. We found that Cdk1 phosphorylated the transcription factor FOXO1 at Ser249 in vitro and in vivo. The phosphorylation of FOXO1 at Ser249 disrupted FOXO1 binding with 14-3-3 proteins and thereby promoted the nuclear accumulation of FOXO1 and stimulated FOXO1-dependent transcription, leading to cell death in neurons. In proliferating cells, Cdk1 induced FOXO1 Ser249 phosphorylation at the G2/M phase of the cell cycle, resulting in FOXO1-dependent expression of the mitotic regulator Polo-like kinase (Plk). These findings define a conserved signaling link between Cdk1 and FOXO1 that may have a key role in diverse biological processes, including the degeneration of postmitotic neurons. [ABSTRACT FROM AUTHOR]

A change in the efficiency of synaptic communication between neurons is thought to underlie learning. Consistent with recent studies of such changes, we find that long-lasting potentiation of synaptic transmission between cultured hippocampal neurons is accompanied by an increase in the number of dusters of postsynaptic glutamate receptors containing the subunit GLuR1. In addition, potentiation is accompanied by a rapid and long-lasting increase in the number of dusters of the presynaptic protein synaptophysin and the number of sites at which synaptophysin and GluR1 are colocalized. These results suggest that potentiation involves rapid coordinate changes in the distribution of proteins in the presynaptic neuron as well as the postsynaptic neuron. [ABSTRACT FROM AUTHOR]

Studies the role of huntingtin activity in striatal neurons that selectively die in Huntington's disease. Functions of the protein; Mutation of huntingtin in Huntington's disease; Involvement in the upregulation of the transcription of brain-derived neurotrophic factor.

To assess the role of BAX in drug-induced apoptosis in human colorectal cancer cells, we generated cells that tack functional BAX genes. Such cells were partially resistant to the apoptotic effects of the chemotherapeutic agent 5-fluorouracil, but apoptosis was not abolished. In contrast, the absence of BAX completely abolished the apoptotic response to the chemopreventive agent sulindac and other nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs inhibited the expression of the antiapoptotic protein Bcl-X[sub L], resulting in an altered ratio of BAX to Bcl-X[sub L] and subsequent mitochondria-mecliated cell death. These results establish an unambiguous role for BAX in apoptotic processes in human epithelial cancers and may have implications for cancer chemoprevention strategies. [ABSTRACT FROM AUTHOR]

Discusses a research on the encoding of potassium channel protein by chlorella virus PBCV-1. Functions of potassium channels in eukaryotes and eukaryotes; Methodology used in the research; Findings of the research.

Discusses a research on a transmembrane protein, designated as calcyon, that is characterized to interact with D1 dopamine receptor. Information on dopamine; Methodology used in the research; Findings of the research.

Shows that strains producing the Helicobacter pylori CagA antigen translocate the bacterial protein CagA into gastric epithelial cells by a secretion system. How the direct biochemical evidence for the residence of CagA was obtained; Mechanics of protein secretion; Putative tyrosine phosphorylation motifs that were identified in the protein sequence.

Presents research which concluded that tumors begin to grow by coopting existing host blood vessels. Contradiction of the view that tumors begin as avascular masses; Role of angiogenesis in the tumor growth process; Effects of the expression of proteins on the balance between vascular regression and growth.

Presents research which examined the effects of suppressing the expression of the N-methyl-D-aspartate receptor (NMDAR) scaffolding protein PSD-95. Role of NMDARs in intracellular signaling pathways; Impact of the suppression on NMDAR function; Effects of suppressing PSD-95; Role of PSD-95 for efficient coupling of NMDAR activity to nitric oxide toxicity and in excitotoxic Ca2+ signaling.

Discusses research which studied the role of transcriptional coregulators in cell development. Differences in extracellular signaling molecules; Determination of threshold responses; Patterns of gene expression; Various mechanisms for cell regulation; Role of coregulatory proteins; Communication between regulatory proteins and the core RNA polymerase II transcription complex.

Examines the importance of the Axin family of proteins in Wnt/Wingless signaling in Drosophila. Role of Wnt/Wingless in cell development; Effect of Wnt/Wingless signaling; Interaction of the Drosophila protein D-Axin with Armadillo and D-APC; Impact of the mutation of D-Axin; Ectopic expression of D-Axin inhibiting Wingless signaling.

Presents research which examined the regulation of responses of immunoglobulin G (IgG) to glycosylphosphatidylinositol (GPI)-anchored protein antigens. Requirements of IgG responses; Regulation of the CD1-NKT cell pathway in Plasmodium and Trypanosoma; Mechanism for antibody responses to diverse pathogens.

Presents research which analyzed the role of signal transducer and activator of transcription (STAT) proteins in T cell receptor (TCR) signaling. Phosphorylation of STAT5; Expression of the protein tyrosine kinase Lck; Role of Lck in STAT5 activation; Stimulation of T cell clones and primary T cell lines; Inhibition of STAT5 function; TCR stimulation activating STAT5; Role of STAT5.

Presents research which showed the role of the protein CmPP16 from Cucurbita maxima. Properties of CmPP16 similar to viral movement proteins; Presence of CmPP16 mRNA in phloem tissue; CmPP16 confined to sieve elements (SE); Results of microinjection and grafting studies about the movement of CmPP16; CmPP16's characteristics; Movement of RNA in the phloem as a part of plant communication.

Presents research which showed the GBR1-related protein GBR2 to be coexpressed with GBR1 in many brain regions. Identification of GBR1; Interaction locus for GBR1 and GBR2; Effects of heterologously expressed GBR2; Activation of potassium channels by GABA B receptor agonists; Importance of the interaction of these receptors related to GABA and receptor signaling pathways.

Presents research which tested mice lacking the cryptochrome 2 blue-light photoreceptor gene (mCry2) for circadian clock-related functions. What cryptochromes are; Traits of mutant mice; Intrinsic circadian period of the mice; CRY2 protein modulating circadian responses; Role of cryptochromes in circadian photoreception in animals.

Presents research which identified and localized the protein tankyrase to human telomeres. Tankyrase binding; Tankyrase containing 24 ankyrin repeats; Traits of recombinant tankyrase; Effects of adenosine diphosphate(ADP)-ribosylation of TRF1; Telomere function in human cells regulated by poly(ADP-ribosyl)ation.

Describes the role of Bcl-2 and related cytoplasmic proteins in the regulation of apoptosis. Promotion of cell survival; Determination of cell fate; Importance of Bcl-2 family members; Opposing factions in the family; Apoptosis mechanisms; Caspase-independent death; Physiological roles; Cell cycle impact; Involvement in cancer; Further research.

Presents research which showed that the POU domain protein Nubbin contributes to the formation of a sharp dorsoventral boundary in the Drosophila wing. Cell interactions mediated by Notch-family receptors; Expression of Botch ligands; Importance of tightly localized activation of Notch; Details about the role of Nubbin in Notch activity.

Presents research which showed that the Sec61 oligomer is attached to the large ribosomal subunit by a single connection in protein transport across the endoplasmic reticulum. Use of purified yeast Sec61 complex; Use of cryo-electron microscopy and reconstruction; Funnel-shaped pore in Sec61 oligomer.

Presents research which explored the role of scaffold, anchoring, and adaptor proteins that contribute to the specificity of signal transduction events. Relaying extracellular signals to intracellular sites and cellular regulation; Workings of signaling pathways; Regulatory mechanisms to influence protein kinases and phosphatases in cells; More.

Presents research which identified a membrane-bound component of the ubiquitin system, Cue1p. Mediation of endoplasmic reticulum (ER) degradation of aberrant proteins; Role of Cue1p; Absence of Cue1p; Requirements for retrograde transport of lumenal substrates; Implications of results.

Presents research which identified Cdc20 and Cdh1 proteins as limiting, substrate-specific activators of anaphase-promoting complex (APC)-dependent proteolysis. Role of proteolysis mediated by APC; Roles of Cdc20 and cdh1 Delta mutants; Overexpression of either CDC20 or CDH1.

Informs that uteroglobin, a steroid-inducible secreted protein, is essential for maintaining normal renal function in mice. Mice with a disrupted uteroglobin gene experiencing severe renal disease that was associated with massive glomerular deposition of predominantly multimeric fibronectin (Fn); Molecular mechanisms; Possibility that an analogous pathogenic mechanism may underlie genetic Fn-deposit human glomerular disease.

Reports that the protein GRP1 and cytohesin-1 appear to connect receptor-activated phosphoinositide (PI) 3-kinase signalling pathways with proteins that mediate biological responses such as cell adhesion and membrane trafficking. Activation of PI 3-kinases by cell surface receptor signal transmission; Research details.

Reports that nuclei of adenomatous polyposis coli (APC)-/- colon carcinoma cells were found to contain a stable beta-catenin-hTcf-4 complex that was constitutively active. Conclusion that constitutive transcription of Tcf target genes, caused by loss of APC function, may be a crucial event in the early transformation of colonic epithelium.

Shows that messenger RNA translation, rather than splicing, is severely impaired in two newly isolated ded1 conditional genetic mutants. The implication of the DED1 gene in nuclear pre-messenger RNA splicing in the yeast Saccharomyces serevisiae; Possible role of the protein Ded1 in the initiation step of messenger RNA translation, as is the distinct DEAD-box protein, eukaryotic initiation factor 4A (aLF4A); Evolutionary conservation of Ded1.

States that the gene encoding intestinal trefoil factor (IFT) was rendered nonfunctional in mice targeted for disruption. The largely unidentified mechanisms that maintain the epithelial integrity of the gastrointestinal tract; Conclusion revealing a central role for ITF in the maintenance and repair of the intestinal mucosa; Details of the research.

Reports on the inactivation of the mouse pS2 (mpS2) gene in order to determine the function of the pS2 trefoil protein, which is normally expressed in the gastric mucosa. Conclusion that mpS2 is essential for normal differentiation of the antral and pyloric gastric mucosa and may function as a gastric-specific tumor suppressor gene; Details of the study.

Discusses the identification of hSRP1alpha as a functional receptor for nuclear localization sequences. Energy-independent docking of the substrate to the nuclear envelope; Translocation through the nuclear pore complex; Nucleotide and deduced amino acid sequence of hSRP1alpha.

Studies the entry of segments of preproteins of defined lengths into the matrix space of mitochondria. Interaction of Hsp70 with proteins emerging from the protein import channel; Steps in the transfer of preproteins from the cytosol into the matrix; Reversibility of translocation.

Many pathogenic bacteria use injectisomes to deliver effector proteins into host cells through type III secretion. Injectisomes consist of a basal body embedded in the bacterial membranes and a needle. In Yersinia, translocation of effectors requires the YopB and YopD proteins, which form a pore in the target cell membrane, and the LcrV protein, which assists the assembly of the pore. Here we report that LcrV forms a distinct structure at the tip of the needle, the tip complex. This unique localization of LcrV may explain its crucial role in the translocation process and its efficacy as the main protective antigen against plague. [ABSTRACT FROM AUTHOR]

Prion infectivity is typically restricted to the central nervous and lymphatic systems of infected hosts, but chronic inflammation can expand the distribution of prions. We tested whether chronic inflammatory kidney disorders would trigger excretion of prion infectivity into urine. Urinary proteins from scrapie-infected mice with lymphocytic nephritis induced scrapie upon inoculation into noninfected indicator mice. Prionuria was found in presymptomatic scrapie-infected and in sick mice, whereas neither prionuria nor urinary PrP[sup Sc] was detectable in prion-infected wild-type or PrP[sup C]-overexpressing mice, or in nephritic mice inoculated with noninfectious brain. Thus, urine may provide a vector for horizontal prion transmission, and inflammation of excretory organs may influence prion spread. [ABSTRACT FROM AUTHOR]

Surveys research done to study the Golgi apparatus. Work based on research by Italian biologist Camillo Golgi; Role of the Golgi apparatus in processing and transporting synthesized proteins; Structure of the Golgi including sacs called cisternae; Relation of the Golgi to the endoplasmic reticulum; Debate about how proteins pass across the Golgi; The cisternal maturation model of the dynamic Golgi; Implications of research.

Discusses the role of glycine receptors in synapse formation. Integration of neuronal signals in synaptic connections; Receptor-associated proteins and neurotransmitters; Research by J.R. Sanes and H. Betz in this issue; The protein gephyrin's role in the formation of inhibitory synapses in the spinal cord and brain; Link between gephyrin and neurological diseases; What glycine receptors are; Traits of mutant mice lacking gephyrin.

Presents research which examined the role of the pro-apoptotic protein CED-4 in the activation of apoptosis. Study of Caenorhabditis elegans; Mediation by protein-protein interaction; Induction of caspase activation and cell death; Oligomerization of CED-4; Mutations that abolished CED-4 oligomerization; Inhibition of this oligomerization.

Presents research which studied the guanine nucleotide exchange factor (GEF) for Rho, p115 RhoGEF. Relations between the regulators of G protein signaling (RGS) family, guanosine triphosphatase (GTPase), and G proteins; Activity of GEF toward subunits of the G proteins G12 and G13; GEF an intermediary in the regulation of Rho proteins by G12 and G13.

Presents research which showed RAG proteins reversing the cleavage reaction by joining a recombination signal sequence (RSS) to a broken coding sequence end. How the assembly of immunoglobulin and T cell receptor genes from separate gene segments begins; Role of RAG1 and RAG2 proteins; Explanation for hybrid joints.

Presents research which isolated and characterized a protein named PIAS3 (protein inhibitor of activated STAT) that binds to Stat3. Activation of signal transducer and activator of transcription-3 (Stat3); Association of PIAS3 with Stat3; Roles of PIAS3 and Stat1; Implications of results.

Informs that signal transducers and activators of transcription (STAT3) proteins, transcription factors for acute phase response genes, act as adapter molecules in signal transduction from the type I interferon receptor. Description of the signal transduction; The p85 regulatory subunit of phosphatidylinositol 3-kinase binding to phosphorylated STAT3 and subsequently undergoing tyrosine phosphorylation; Implications.

States that the protein hFz5, a member of the Frizzled family of seven-transmembrane receptors, mediates axis induction in Xenopus laevis embryos by the Wingless/Wnt-1 subclass of Wnt molecules. Differences between the Wingless/Wnt-1 subclasses and the Wingless/Wnt-5A subclasses; Wnt-5A inducing axis duplication and an ectopic Spemann organizer in the presence of hFz5; Antagonizing of Wnt-5A/hFz5 signalling.

Notes that the nuclear factor of activated T cells (NF-AT)-driven interleukin-4 cytokine promoter-mediated transcription is potentiated by the NF-AT interacting protein (NIP45). Role of NF-AT in mediating the induction of cytokine gene transcription; Identification of NIP45; Transcripts encoding NIP45; Implications.

Examines the structure and function of trimeric maltoporin protein (LamB) located in the lipid bilayer of the bacterium Escherichia coli. Facilitation of the diffusion of maltodextrins across the outer membrane of the bacterium; Crystal structure of the protein; Protein conformation; Translocation of oligosaccahrides across the membrane by guided diffusion.

The article discusses research on the role that the perineuronal nets (PNNs), which consist of proteins and sugars, around brain cells play in the storing of long-term memory, referencing a study led by neuroscientist Sakina Palida. An overview of the role that PNNs play in the controlling the functioning and formation of synapses is provided.

The article discusses the mechanism of the circadian cycle involving the proteins cryptochrome and period. According to the author, certain proteins require to be regulated at a precise manner which applies to certain components of the circadian clock. Moreover, the author indicates that most physiological processes in mammals are influenced by the circadian clock. A discussion on the rhythm-generating molecular circuitry in hypothalamic neurons and peripheral cells involving the Cry and Per proteins is presented. Furthermore, the mechanism and function of the proteasome in the identification and decay of the accumulated Cry protein is illustrated.

Reports on the effects of mutant huntingtin protein on cortical neurons producing brain-derived neurotrophic factor. Importance of BDNF in the survival of striatal neurons; Functions of huntingtin; Role of BDNF in the maintenance of nerve cells.

Describes research which studied the role of the protein Ran in mitosis. Versatility of the protein; Role in cell division; Traits of cells with faulty Ran genes; Work of Nishimoto et al in this issue regarding Ran in spindle formation; Previous research; Criticism of research.