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101.
Ito A Tauchi H Kobayashi J Morishima K Nakamura A Hirokawa Y Matsuura S Ito K Komatsu K 《Biochemical and biophysical research communications》1999,265(3):716-721
Cells from Nijmegen breakage syndrome (NBS) display multiple phenotypes, such as chromosomal instability, hypersensitivity to cell killing from ionizing radiation, and possibly abnormal cell cycle checkpoints. NBS1, a gene mutated in NBS patients, appears to encode a possible repair protein, which could form the foci of a sensor-like molecular complex capable of detecting DNA double strand breaks, however, it has no kinase domain for signaling DNA damage. Here, we report that the stable expression of NBS1 cDNA in NBS cells after transfection results in the complete restoration of foci formation in the nucleus, and in normal cell survival after irradiation. The prolonged G2 block observed after irradiation was also abolished by expression of NBS1, providing additional confirmation that the G2 checkpoint is abrogated in NBS cells. These results suggest that a defective NBS1 protein could be the sole cause of the NBS phenotype, and that NBS1 likely interacts with another protein(s) to produce the entire range of NBS phenotypic expression. 相似文献
102.
BACKGROUND: There have been only 4 reported cases of cribriform-morular variant of papillary thyroid carcinoma (CMVPTC) with cytologic findings from fine needle aspiration. In these reports, the cytologic findings do not fully reflect the histologic characteristics of this entity. We report a case of CMVPTC in which a cribriform pattern without colloid and epithelial morules with peculiar nuclear clearing (PNC) were present in smears, thus fulfilling the criteria for a cytologic diagnosis of CMVPTC. Protein truncation tests for APC molecule abnormality indicated the presence of germline mutation in the patient's APC gene. CASE: A 30-year-old woman had multiple thyroid tumors. Aspiration cytology revealed a large number of round to spindle-shaped atypical-cells showing sheet-like, cribriform, follicular, whorl-like and solid, 3-dimensional arrangements. The cribriform and follicular arrangements did not contain colloid in the lumen. The powdery chromatin pattern characteristic of papillary carcinoma was not observed, but there were scattered intranuclear cytoplasmic pseudoinclusions and grooved nuclei. The nuclei of the atypical cells presenting in the whorl formations showed enlargement, thickened nuclear membranes and entirely clear contents, consistent with PNC. Hyalinelike necrotic cells were also observed in the cell clusters or in the background. Histologic and immunohistochemical findings were typical of CMVPTC. CONCLUSION: The cribriform pattern without colloid, fascicular or whorl formation of spindle cells, and morules with PNC are identifiable on cytologic smears and are sufficiently distinctive to allow a cytologic diagnosis of CMVPTC. 相似文献
103.
Oyama F Kotliarova S Harada A Ito M Miyazaki H Ueyama Y Hirokawa N Nukina N Ihara Y 《The Journal of biological chemistry》2004,279(26):27272-27277
A series of observations have indicated that tau, one of the major microtubule-associated proteins, is involved in neuronal cell morphogenesis and axonal maintenance. Tau is also the major component of paired helical filaments found in brains affected by Alzheimer's disease. To explore an as yet unidentified role of tau in vivo, approximately 11,000 mRNAs were profiled from tau-deficient mouse brains and compared with those from control brains at the same ages. The expression of Gem GTPase, a small GTP-binding protein of the ras superfamily, was significantly increased in the brains of tau-deficient mice at 8 weeks of age. Because Gem GTPase is a negative regulator of the Rho-Rho kinase pathway for cytoskeletal organization, this protein was transiently overexpressed in Chinese hamster ovary cells that do not express tau. Overexpression of Gem GTPase induced a marked elongation of Chinese hamster ovary cells, and simultaneous expression of tau eliminated this effect, although tau did not bind directly to Gem GTPase. This anti-elongation activity of tau was attributed to its microtubule-binding domain, and homologous domains of microtubule-associated proteins 2 and 4 exhibited similar antagonistic activities. Taken together, the present results indicate that the level of Gem GTPase and its cell elongation activity are modulated by tau and suggest that tau may be involved in a Gem GTPase-mediated signal transduction pathway. 相似文献
104.
Temperature-sensitive mutation in yeast mitochondrial ribosome recycling factor (RRF) 总被引:4,自引:1,他引:3
Teyssier E Hirokawa G Tretiakova A Jameson B Kaji A Kaji H 《Nucleic acids research》2003,31(14):4218-4226
The yeast protein Rrf1p encoded by the FIL1 nuclear gene bears significant sequence similarity to Escherichia coli ribosome recycling factor (RRF). Here, we call FIL1 Ribosome Recycling Factor of yeast, RRF1. Its gene product, Rrf1p, was localized in mitochondria. Deletion of RRF1 leads to a respiratory incompetent phenotype and to instability of the mitochondrial genome (conversion to rho–/rho0 cytoplasmic petites). Yeast with intact mitochondria and with deleted genomic RRF1 that harbors a plasmid carrying RRF1 was prepared from spores of heterozygous diploid yeast. Such yeast with a mutated allele of RRF1, rrf1-L209P, grew on a non-fermentable carbon source at 30 but not at 36°C, where mitochondrial but not total protein synthesis was 90% inhibited. We propose that Rrf1p is essential for mitochondrial protein synthesis and acts as a RRF in mitochondria. 相似文献
105.
Kinesin transports RNA: isolation and characterization of an RNA-transporting granule 总被引:38,自引:0,他引:38
RNA transport is an important and fundamental event for local protein synthesis, especially in neurons. RNA is transported as large granules, but little is known about them. Here, we isolated a large RNase-sensitive granule (size: 1000S approximately) as a binding partner of conventional kinesin (KIF5). We identified a total of 42 proteins with mRNAs for CaMKIIalpha and Arc in the granule. Seventeen of the proteins (hnRNP-U, Pur alpha and beta, PSF, DDX1, DDX3, SYNCRIP, TLS, NonO, HSPC117, ALY, CGI-99, staufen, three FMRPs, and EF-1alpha) were extensively investigated, including their classification, binding combinations, and necessity for the "transport" of RNA. These proteins and the mRNAs were colocalized to the kinesin-associated granules in dendrites. The granules moved bidirectionally, and the distally directed movement was enhanced by the overexpression of KIF5 and reduced by its functional blockage. Thus, kinesin transports RNA via this granule in dendrites coordinately with opposite motors, such as dynein. 相似文献
106.
Alterations of structure and hydrolase activity of parkinsonism-associated human ubiquitin carboxyl-terminal hydrolase L1 variants 总被引:9,自引:0,他引:9
Nishikawa K Li H Kawamura R Osaka H Wang YL Hara Y Hirokawa T Manago Y Amano T Noda M Aoki S Wada K 《Biochemical and biophysical research communications》2003,304(1):176-183
Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is a neuron-specific ubiquitin recycling enzyme. A mutation at residue 93 and polymorphism at residue 18 within human UCH-L1 are linked to familial Parkinson's disease and a decreased Parkinson's disease risk, respectively. Thus, we constructed recombinant human UCH-L1 variants and examined their structure (using circular dichroism) and hydrolase activities. We confirmed that an I93M substitution results in a decrease in kcat (45.6%) coincident with an alteration in alpha-helical content. These changes may contribute to the pathogenesis of Parkinson's disease. In contrast, an S18Y substitution results in an increase in kcat (112.6%) without altering the circular dichroistic spectrum. These data suggest that UCH-L1 hydrolase activity may be inversely correlated with Parkinson's disease risk and that the hydrolase activity is protective against the disease. Furthermore, we found that oxidation of UCH-L1 by 4-hydroxynonenal, a candidate for endogenous mediator of oxidative stress-induced neuronal cell death, results in a loss of hydrolase activity. Taken together, these results suggest that further studies of altered UCH-L1 hydrolase function may provide new insights into a possible common pathogenic mechanism between familial and sporadic Parkinson's disease. 相似文献
107.
108.
Microtubules provide directional cues for polarized axonal transport through interaction with kinesin motor head 总被引:8,自引:0,他引:8
Post-Golgi carriers of various newly synthesized axonal membrane proteins, which possess kinesin (KIF5)-driven highly processive motility, were transported from the TGN directly to axons. We found that KIF5 has a preference to the microtubules in the initial segment of axon. Low dose paclitaxel treatment caused missorting of KIF5, as well as axonal membrane proteins to the tips of dendrites. Microtubules in the initial segment of axons showed a remarkably high affinity to EB1-YFP, which was known to bind the tips of growing microtubules. These findings revealed unique features of the microtubule cytoskeletons in the initial segment, and suggested that they provide directional information for polarized axonal transport. 相似文献
109.
Takahashi J Fujiwara S Kikyo M Hirokawa Y Tsuzuki M 《Marine biotechnology (New York, N.Y.)》2002,4(1):94-101
We investigated the extent of calcification on the cell surface of the coccolithophorid Pleurochrysis haptonemofera using flow cytometry. Side scattering (SSC) by coccolith-bearing cells was higher than that by naked cells, suggesting the
difference was due to scattering of the laser beam by the coccoliths. SSC of coccolith-bearing cells under acidic conditions
corresponded well to the extracellular Ca content, although SSC could not be used to detect a delicate change in the coccolith
thickness. The increase in SSC during the reproduction of coccoliths after decalcification was consistent with the increase
in the number of coccoliths on the cell surface. The fluorescence after fluorescein-isothiocyanate-labeled lectin staining
suggests that α-d-mannose, α-d-glucose, d-galactose, d-N-acetylgalactosamine, or derivatives of them are included in the coccoliths. Measurement of SSC and fluorescence after fluorescein-isothiocyanate-labeled
lectin staining enabled rapid and quantitative determination of the status on the cell surface and isolation of desirable
cells for physiological studies by cell sorting.
Received May 22, 2001; accepted July 30, 2001. 相似文献
110.
Yoshiaki Yonekawa Akihiro Harada Yasushi Okada Takeshi Funakoshi Yoshimitsu Kanai Yosuke Takei Sumio Terada Tetsuo Noda Nobutaka Hirokawa 《The Journal of cell biology》1998,141(2):431-441
The nerve axon is a good model system for studying the molecular mechanism of organelle transport in cells. Recently, the new kinesin superfamily proteins (KIFs) have been identified as candidate motor proteins involved in organelle transport. Among them KIF1A, a murine homologue of unc-104 gene of Caenorhabditis elegans, is a unique monomeric neuron– specific microtubule plus end–directed motor and has been proposed as a transporter of synaptic vesicle precursors (Okada, Y., H. Yamazaki, Y. Sekine-Aizawa, and N. Hirokawa. 1995. Cell. 81:769–780). To elucidate the function of KIF1A in vivo, we disrupted the KIF1A gene in mice. KIF1A mutants died mostly within a day after birth showing motor and sensory disturbances. In the nervous systems of these mutants, the transport of synaptic vesicle precursors showed a specific and significant decrease. Consequently, synaptic vesicle density decreased dramatically, and clusters of clear small vesicles accumulated in the cell bodies. Furthermore, marked neuronal degeneration and death occurred both in KIF1A mutant mice and in cultures of mutant neurons. The neuronal death in cultures was blocked by coculture with wild-type neurons or exposure to a low concentration of glutamate. These results in cultures suggested that the mutant neurons might not sufficiently receive afferent stimulation, such as neuronal contacts or neurotransmission, resulting in cell death. Thus, our results demonstrate that KIF1A transports a synaptic vesicle precursor and that KIF1A-mediated axonal transport plays a critical role in viability, maintenance, and function of neurons, particularly mature neurons. 相似文献