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981.
Yuuki Fujiwara Akiko Furuta Hisae Kikuchi Shu Aizawa Yusuke Hatanaka Chiho Konya Kenko Uchida Aya Yoshimura Yoshitaka Tamai Keiji Wada Tomohiro Kabuta 《Autophagy》2013,9(3):403-409
Regulated degradation of cellular components by lysosomes is essential to maintain biological homeostasis. In mammals, three forms of autophagy, macroautophagy, microautophagy and chaperone-mediated autophagy (CMA), have been identified. Here, we showed a novel type of autophagy, in which RNA is taken up directly into lysosomes for degradation. This pathway, which we term “RNautophagy,” is ATP-dependent, and unlike CMA, is independent of HSPA8/Hsc70. LAMP2C, a lysosomal membrane protein, serves as a receptor for this pathway. The cytosolic tail of LAMP2C specifically binds to almost all total RNA derived from mouse brain. The cytosolic sequence of LAMP2C and its affinity for RNA are evolutionarily conserved from nematodes to humans. Our findings shed light on the mechanisms underlying RNA homeostasis in higher eukaryotes. 相似文献
982.
983.
Kozlov SV Graham ME Jakob B Tobias F Kijas AW Tanuji M Chen P Robinson PJ Taucher-Scholz G Suzuki K So S Chen D Lavin MF 《The Journal of biological chemistry》2011,286(11):9107-9119
The recognition and signaling of DNA double strand breaks involves the participation of multiple proteins, including the protein kinase ATM (mutated in ataxia-telangiectasia). ATM kinase is activated in the vicinity of the break and is recruited to the break site by the Mre11-Rad50-Nbs1 complex, where it is fully activated. In human cells, the activation process involves autophosphorylation on three sites (Ser(367), Ser(1893), and Ser(1981)) and acetylation on Lys(3016). We now describe the identification of a new ATM phosphorylation site, Thr(P)(1885) and an additional autophosphorylation site, Ser(P)(2996), that is highly DNA damage-inducible. We also confirm that human and murine ATM share five identical phosphorylation sites. We targeted the ATM phosphorylation sites, Ser(367) and Ser(2996), for further study by generating phosphospecific antibodies against these sites and demonstrated that phosphorylation of both was rapidly induced by radiation. These phosphorylations were abolished by a specific inhibitor of ATM and were dependent on ATM and the Mre11-Rad50-Nbs1 complex. As found for Ser(P)(1981), ATM phosphorylated at Ser(367) and Ser(2996) localized to sites of DNA damage induced by radiation, but ATM recruitment was not dependent on phosphorylation at these sites. Phosphorylation at Ser(367) and Ser(2996) was functionally important because mutant forms of ATM were defective in correcting the S phase checkpoint defect and restoring radioresistance in ataxia-telangiectasia cells. These data provide further support for the importance of autophosphorylation in the activation and function of ATM in vivo. 相似文献
984.
985.
Mitsui K Koshimura Y Yoshikawa Y Matsushita M Kanazawa H 《The Journal of biological chemistry》2011,286(43):37625-37638
Multivesicular bodies (MVBs) are late endosomal compartments containing luminal vesicles (MVB vesicles) that are formed by inward budding of the endosomal membrane. In budding yeast, MVBs are an important cellular mechanism for the transport of membrane proteins to the vacuolar lumen. This process requires a class E subset of vacuolar protein sorting (VPS) genes. VPS44 (allelic to NHX1) encodes an endosome-localized Na(+)/H(+) exchanger. The function of the VPS44 exchanger in the context of vacuolar protein transport is largely unknown. Using a cell-free MVB formation assay system, we demonstrated that Nhx1p is required for the efficient formation of MVB vesicles in the late endosome. The recruitment of Vps27p, a class E Vps protein, to the endosomal membrane was dependent on Nhx1p activity and was enhanced by an acidic pH at the endosomal surface. Taken together, we propose that Nhx1p contributes to MVB formation by the recruitment of Vps27p to the endosomal membrane, possibly through Nhx1p antiporter activity. 相似文献
986.
Heni Susilowati Hirohiko Okamura Katsuhiko Hirota Masayuki Shono Kaya Yoshida Keiji Murakami Atsushi Tabata Hideaki Nagamune Tatsuji Haneji Yoichiro Miyake 《Biochemical and biophysical research communications》2011,404(1):57
Intermedilysin (ILY) is a cholesterol-dependent cytolysin produced by Streptococcus intermedius, which is associated with human brain and liver abscesses. Although intrahepatic bile duct cells play a valuable role in the pathogenesis of liver abscess, the molecular mechanism of ILY-treated intrahepatic bile duct cells remains unknown. In this study, we report that ILY induced a nuclear accumulation of intracellular calcium ([Ca2+]i) in human cholangiocellular cells HuCCT1. We also demonstrate that 10 ng/ml ILY induced NFAT1 dephosphorylation and its nuclear translocation in HuCCT1 cells. In contrast to the result that ILY induced NF-κB translocation in human hepatic HepG2 cells, ILY did not affect NF-κB localization in HuCCT1 cells. Dephosphorylation and nuclear translocation of NFAT1 caused by ILY were prevented by [Ca2+]i calcium chelator, BAPTA/AM, and calcineurin inhibitors, cyclosporine A and tacrolimus. ILY induced early growth response-1 (EGR-1) expression and it was inhibited by the pre-treatment with cyclosporine A, indicating that the calcineurin/NFAT pathway was involved in EGR-1 expression in response to ILY. ILY-induced calcineurin/NFAT1 activation and sequential EGR-1 expression might be related to the pathogenesis of S. intermedius in human bile duct cells. 相似文献
987.
988.
Nakamura T Tonozuka T Ito S Takeda Y Sato R Matsuo I Ito Y Oguma K Nishikawa A 《Archives of biochemistry and biophysics》2011,(1):69-77
A critical role in internalizing the Clostridium botulinum neurotoxin into gastrointestinal cells is played by nontoxic components complexed with the toxin. One of the components, a β-trefoil lectin has been known as HA33 or HA1. The HA33 from C. botulinum type A (HA33/A) has been predicted to have a single sugar-binding site, while type C HA33 (HA33/C) has two sites. Here we constructed HA33/C mutants and evaluated the binding capacities of the individual sites through mucin-assay and isothermal titration calorimetry. The mutant W176A (site I knockout) had a Kd value of 31.5 mM for galactose (Gal) and 61.3 mM for N-acetylgalactosamine (GalNAc), while the Kd value for N-acetylneuraminic acid (Neu5Ac) was too high to be determined. In contrast, the double mutant N278A/Q279A (site II knockout) had a Kd value of 11.8 mM for Neu5Ac. We also determined the crystal structures of wild-type and the F179I mutant in complex with GalNAc at site II. The results suggest that site I of HA33/C is quite unique in that it mainly recognizes Neu5Ac, and site II seems less important for the lectin specificity. The architectures and the properties of the sugar-binding sites of HA33/C and HA33/A were shown to be drastically different. 相似文献
989.
A method for screening lectin-producing microorganisms was developed. The presence of lectin on microbial cell surfaces was used as an index for their selective isolation. The lectin-producing microorganisms adhered to sugar-modified agarose beads and were selectively eluted with specific saccharide solutions. Spin columns were an effective tool for excluding non-lectin producers. Eighty-seven percent of the microorganisms that were eluted from the beads showed hemagglutination. The results of sequence analysis indicated that some of the eluted microorganisms have not been previously identified as lectin-producing microorganisms. 相似文献
990.
Compression wood (CW) tracheids have different cell wall components than normal wood (NW) tracheids. However, temporal and
spatial information on cell wall components in CW tracheids is poorly understood. We investigated the distribution of arabino-4-O-methylglucuronoxylans (AGXs) and O-acetyl-galactoglucomannans (GGMs) in differentiating CW tracheids. AGX labeling began to be detected in the corner of the
S1 layer at the early S1 formation stage. Subsequently, the cell corner middle lamella (ccML) showed strong AGX labeling when intercellular spaces
were not fully formed. AGX labeling was uniformly distributed in the S1 layer, but showed uneven distribution in the S2 layer. AGX labeling was mainly detected in the inner S2 layer after the beginning of the helical cavity formation. The outer S2 layer showed almost no labeling of low substituted AGXs. Only a very small amount of high substituted AGXs was distributed
in the outer S2 layer. These patterns of AGX labeling in the S2 layer opposed the lignin and β-1-4-galactan distribution in CW tracheids. GGM labeling patterns were almost identical to
AGX labeling in the early stages of CW tracheids, and GGM labeling was detected in the entire S2 layer from the early S2 formation stage of CW tracheids with some spatial differences in labeling density depending on developmental stage. Compared
with NW tracheids, CW tracheids showed significantly different AGX distributions in the secondary cell wall but similar GGM
labeling patterns. No significant differences were observed in labeling after delignification of CW tracheids. 相似文献