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451.
452.
Fujitani M Kawai H Proia RL Kashiwagi A Yasuda H Yamashita T 《Journal of neurochemistry》2005,94(1):15-21
Myelin-associated glycoprotein (MAG) is a potent inhibitor of neurite outgrowth from a variety of neurons. Here we show that gangliosides, GT1b and GD1a, as well as the Nogo receptor, are functional binding partners for soluble MAG-Fc. Postnatal cerebellar neurons from mice deficient in the GalNAcT gene are insensitive to MAG with regard to neurite outgrowth and lack in the activation of RhoA. MAG-Fc or the antibody to GT1b and GD1a elicits recruitment of p75(NTR.) to lipid rafts, specialized microdomain for signal transduction. Disruption of lipid rafts results in abolishment of inhibitory effects of MAG-Fc and the Nogo peptide. These findings establish gangliosides as functional binding partners for soluble MAG. Gangliosides may play a role in translocation of p75(NTR.) to lipid rafts for initiation of the signal transduction. 相似文献
453.
Miyake S Yamashita T Taniguchi M Tamatani M Sato K Tohyama M 《Biochemical and biophysical research communications》2002,295(2):463-468
Here we report the identification and functional characterization of a novel mitochondrial tricarboxylate carrier protein, designated BBG-TCC, in rat brain. The cDNA encodes the predicted protein of 342-amino acid residues with five putative membrane-spanning domains. The protein has apparent similarity with a mitochondrial tricarboxylate carrier TCC, but is distinct from the other mitochondria anion transporters. BBG-TCC shows a citrate transport activity. It is specifically expressed in the brain and localizes in the mitochondria of Bergmann glial cells. In contrast, the expression of TCC is rather ubiquitous and strong in neuronal cells in the brain. This new family of proteins may contribute to biosynthesis and bioenergetics in the brain. 相似文献
454.
Kato U Emoto K Fredriksson C Nakamura H Ohta A Kobayashi T Murakami-Murofushi K Kobayashi T Umeda M 《The Journal of biological chemistry》2002,277(40):37855-37862
Ro09-0198 (Ro) is a tetracyclic peptide antibiotic that binds specifically to phosphatidylethanolamine (PE) and causes cytolysis. To investigate the molecular basis of transbilayer movement of PE in biological membranes, we have isolated a series of budding yeast mutants that are hypersensitive to the Ro peptide. One of the most sensitive mutants, designated ros3 (Ro-sensitive 3), showed no significant change in the cellular phospholipid composition or in the sensitivity to amphotericin B, a sterol-binding polyene macrolide antibiotic. These results suggest that the mutation of ros3 affects the PE organization on the plasma membrane, rather than PE synthesis or overall organization of the membrane structures. By functional complementation screening, we identified the gene ROS3 affected in the mutant, and we showed that the hypersensitive phenotype was caused by the defective expression of the ROS3 gene product, Ros3p, an evolutionarily conserved protein with two putative transmembrane domains. Disruption of the ROS3 gene resulted in a marked decrease in the internalization of fluorescence-labeled analogs of PE and phosphatidylcholine, whereas the uptake of fluorescence-labeled phosphatidylserine and endocytic markers was not affected. Neither expression levels nor activities of ATP-binding cassette transporters of the ros3Delta cells differed from those of wild type cells, suggesting that Ros3p is not related to the multidrug resistance activities. Immunochemical analyses of the structure and subcellular localization showed that Ros3p was a glycosylated membrane protein localized in both the plasma membrane and the endoplasmic reticulum, and that a part of Ros3p was associated with the detergent-insoluble glycolipid-enriched complexes. These results indicate that Ros3p is a membrane glycoprotein that plays an important role in the phospholipid translocation across the plasma membrane. 相似文献
455.
Isaka K Nishi H Nakada T Osakabe Y Hokamura M Serizawa H Ebihara Y Takayama M 《Human cell》2002,15(4):200-206
We present a new cell line, EJ established from an invasive endometrioid adenocarcinoma of the uterine corpus in a 56-year-old patient. The cells show rapid growth in culture with a doubling time of 16 h and high migration activity. Monolayer-cultured cells were polygonal in shape showing a tendency to pile up without contact inhibition. Subcutaneous transplantation of the EJ cells into nude mice formed solid tumors that were histologically diagnosed as adenocarcinoma, whereas no metastasis was observed. Cultured EJ cells produced tissue polypeptide antigen (IPA). Genetic and molecular analyses revealed high telomerase activity but not estrogen receptor alpha expression. Using the DNA sequencing technique, we have screened EJ cells for p53 mutation in exon 5 to 8 but no mutation of p53 was observed. This cell line appears to represent the development of a more malignant clone with divergent receptor function and growth behavior, and provides us with an interesting new tool for the study of tumorigenesis in the human endometrium. 相似文献
456.
Fukata Y Itoh TJ Kimura T Ménager C Nishimura T Shiromizu T Watanabe H Inagaki N Iwamatsu A Hotani H Kaibuchi K 《Nature cell biology》2002,4(8):583-591
Regulated increase in the formation of microtubule arrays is thought to be important for axonal growth. Collapsin response mediator protein-2 (CRMP-2) is a mammalian homologue of UNC-33, mutations in which result in abnormal axon termination. We recently demonstrated that CRMP-2 is critical for axonal differentiation. Here, we identify two activities of CRMP-2: tubulin-heterodimer binding and the promotion of microtubule assembly. CRMP-2 bound tubulin dimers with higher affinity than it bound microtubules. Association of CRMP-2 with microtubules was enhanced by tubulin polymerization in the presence of CRMP-2. The binding property of CRMP-2 with tubulin was apparently distinct from that of Tau, which preferentially bound microtubules. In neurons, overexpression of CRMP-2 promoted axonal growth and branching. A mutant of CRMP-2, lacking the region responsible for microtubule assembly, inhibited axonal growth and branching in a dominant-negative manner. Taken together, our results suggest that CRMP-2 regulates axonal growth and branching as a partner of the tubulin heterodimer, in a different fashion from traditional MAPs. 相似文献
457.
Endotoxic and immunobiological activities of a chemically synthesized lipid A of Helicobacter pylori strain 206-1 总被引:1,自引:0,他引:1
Ogawa T Asai Y Sakai Y Oikawa M Fukase K Suda Y Kusumoto S Tamura T 《FEMS immunology and medical microbiology》2003,36(1-2):1-7
A synthetic lipid A of Helicobacter pylori strain 206-1 (compound HP206-1), which is similar to its natural lipid A, exhibited no or very low endotoxic activities as compared to Escherichia coli-type synthetic lipid A (compound 506). Furthermore, compound HP206-1 as well as its natural lipid A demonstrated no or very low mitogenic responses in murine spleen cell. On the other hand, compound HP206-1 showed a weaker but significant production of interleukin-8 in a gastric cancer cell line, MKN-1, in comparison with compound 506. Furthermore, compound HP206-1 exhibited induction of tumor necrosis factor-alpha production in human peripheral blood mononuclear cells and the cytokine production was clearly inhibited by mouse anti-human Toll-like receptor (TLR) 4 monoclonal antibody HTA125. Our findings indicate that the chemically synthesized lipid A, mimicking the natural lipid A portion of lipopolysaccharide from H. pylori strain 206-1, has a low endotoxic potency and immunobiological activities, and is recognized by TLR4. 相似文献
458.
PKA phosphorylates the p75 receptor and regulates its localization to lipid rafts 总被引:9,自引:0,他引:9
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Although a large number of studies have been carried out on the diverse effects mediated by the common neurotrophin receptor p75(NTR), little is known about the molecular mechanisms by which p75(NTR) initiates intracellular signal transduction. We identified a variant of the beta catalytic subunit of cAMP-dependent protein kinase (PKACbeta) as a p75(NTR)-interacting protein, which phosphorylates p75(NTR) at Ser304. Intracellular cAMP in cerebellar neurons was accumulated transiently by ligand binding to p75(NTR). Activation of cAMP-PKA is required for translocation of p75(NTR) to lipid rafts, and for biochemical and biological activities of p75(NTR), such as inactivation of Rho and the neurite outgrowth. Proper recruitment of activated p75(NTR) to lipid rafts, structures that represent specialized signaling organelles, is of fundamental importance in determining p75(NTR) bioactivity. 相似文献
459.
Yatsushiro S Taniguchi S Mitamura T Omote H Moriyama Y 《Biochimica et biophysica acta》2005,1717(2):89-96
Vacuolar H(+)-ATPase (V-ATPase), an electrogenic proton pump, is highly expressed in Plasmodium falciparum, the human malaria parasite. Although V-ATPase-driven proton transport is involved in various physiological processes in the parasite, the overall features of the V-ATPase of P. falciparum, including the gene organization and biogenesis, are far less known. Here, we report cDNA cloning of proteolipid subunit c of P. falciparum, the smallest and most highly hydrophobic subunit of V-ATPase. RT-PCR analysis as well as Northern blotting indicated expression of the proteolipid gene in the parasite cells. cDNA, which encodes a complete reading frame comprising 165 amino acids, was obtained, and its deduced amino acid sequence exhibits 52 and 57% similarity to the yeast and human counterparts, respectively. Southern blot analysis suggested the presence of a single copy of the proteolipid gene, with 5 exons and 4 introns. Upon transfection of the cDNA into a yeast null mutant, the cells became able to grow at neutral pH, accompanied by vesicular accumulation of quinacrine. In contrast, a mutated proteolipid with replacement of glutamate residue 138 with glutamine did not lead to recovery of the growth ability or vesicular accumulation of quinacrine. These results indicated that the cDNA actually encodes the proteolipid of P. falciparum and that the proteolipid is functional in yeast. 相似文献
460.
Wallerian degeneration involves Rho/Rho-kinase signaling 总被引:6,自引:0,他引:6
Yamagishi S Fujitani M Hata K Kitajo K Mimura F Abe H Yamashita T 《The Journal of biological chemistry》2005,280(21):20384-20388
Local axon degeneration is a common pathological feature of many neurodegenerative diseases, whereas the underlying molecular mechanisms are largely unknown. In this study, we used the degeneration of transected axons, termed "Wallerian degeneration," as a model to examine the possible involvement of Rho. Nogo-66, a myelin-derived inhibitor of axon regeneration, significantly accelerated axon degeneration of the dorsal root ganglion explant in vitro, whereas inhibiting Rho-kinase activity abolished the effect. Rho activation was observed in the distal part of the injured axons after spinal cord injury. We demonstrate that degeneration of the injured cortico-spinal axons was significantly retarded by a Rho-kinase inhibitor in vivo. Our findings suggest that inhibiting the signaling pathway may retard axon degeneration in pathological conditions. 相似文献