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CART: an Hrs/actinin-4/BERP/myosin V protein complex required for efficient receptor recycling 总被引:8,自引:0,他引:8 下载免费PDF全文
Altering the number of surface receptors can rapidly modulate cellular responses to extracellular signals. Some receptors, like the transferrin receptor (TfR), are constitutively internalized and recycled to the plasma membrane. Other receptors, like the epidermal growth factor receptor (EGFR), are internalized after ligand binding and then ultimately degraded in the lysosome. Routing internalized receptors to different destinations suggests that distinct molecular mechanisms may direct their movement. Here, we report that the endosome-associated protein hrs is a subunit of a protein complex containing actinin-4, BERP, and myosin V that is necessary for efficient TfR recycling but not for EGFR degradation. The hrs/actinin-4/BERP/myosin V (CART [cytoskeleton-associated recycling or transport]) complex assembles in a linear manner and interrupting binding of any member to its neighbor produces an inhibition of transferrin recycling rate. Disrupting the CART complex results in shunting receptors to a slower recycling pathway that involves the recycling endosome. The novel CART complex may provide a molecular mechanism for the actin-dependence of rapid recycling of constitutively recycled plasma membrane receptors. 相似文献
126.
Buffie J. Clodfelder Bryan M. Gullick Henry C. Lukaski Yasmin Neggers John B. Vincent 《Journal of biological inorganic chemistry》2005,10(2):119-130
The in vivo effects of gavage administration of the synthetic, functional biomimetic cation [Cr3O(O2CCH2CH3)6(H2O)3]+ to healthy and type 2 diabetic model rats are described. After 24 weeks of treatment (0–1,000 g Cr/kg body mass) of healthy Sprague Dawley rats, the cation results in a lowering (P<0.05) of fasting blood plasma low-density lipoprotein (LDL) cholesterol, total cholesterol, triglycerides, and insulin levels and of 2-h plasma insulin and glucose concentrations after a glucose challenge. Zucker obese rats (a model of the early stages of type 2 diabetes) and Zucker diabetic fatty rats (a model for type 2 diabetes) after supplementation (1,000 g Cr/kg) have lower fasting plasma total, high-density lipoprotein, and LDL cholesterol, triglycerides, glycated hemoglobin, and insulin levels and lower 2-h plasma insulin levels in glucose tolerance tests. The lowering of plasma insulin concentrations with little effect on glucose concentrations suggests that the supplement increases insulin sensitivity. The cation after 12 and 22 or 24 weeks of administration lowers (P<0.05) fasting plasma glycated hemoglobin levels in the Zucker diabetic and Zucker obese rats, respectively, and thus can improve the glucose status of the diabetic models. The effects cannot be attributed to the propionate ligand.Supplementary material is available for this article at .An erratum to this article can be found at 相似文献
127.
Nielsen PR Nietlispach D Buscaino A Warner RJ Akhtar A Murzin AG Murzina NV Laue ED 《The Journal of biological chemistry》2005,280(37):32326-32331
We report here the structure of the putative chromo domain from MOF, a member of the MYST family of histone acetyltransferases that acetylates histone H4 at Lys-16 and is part of the dosage compensation complex in Drosophila. We found that the structure of this domain is a beta-barrel that is distinct from the alpha + beta fold of the canonical chromo domain. Despite the differences, there are similarities that support an evolutionary relationship between the two domains, and we propose the name "chromo barrel." The chromo barrel domains may be divided into two groups, MSL3-like and MOF-like, on the basis of whether a group of conserved aromatic residues is present or not. The structure suggests that, although the MOF-like domains may have a role in RNA binding, the MSL3-like domains could instead bind methylated residues. The MOF chromo barrel shares a common fold with other chromatin-associated modules, including the MBT-like repeat, Tudor, and PWWP domains. This structural similarity suggests a probable evolutionary pathway from these other modules to the canonical chromo domains (or vice versa) with the chromo barrel domain representing an intermediate structure. 相似文献
128.
Harding LP Marshall VM Hernandez Y Gu Y Maqsood M McLay N Laws AP 《Carbohydrate research》2005,340(6):1107-1111
Lactobacillus delbrueckii subsp. bulgaricus NCFB2074 when grown in skimmed milk secretes a highly branched exopolysaccharide. The exopolysaccharide has a heptasaccharide repeat unit and is composed of glucose and galactose in the molar ratio 3:4. Using chemical techniques and 1D and 2D NMR spectroscopy the polysaccharide has been shown to possess the following repeat unit structure: [carbohydrate structure: see text]. 相似文献
129.
Signaling through CD14 attenuates the inflammatory response to Borrelia burgdorferi, the agent of Lyme disease 总被引:3,自引:0,他引:3
Benhnia MR Wroblewski D Akhtar MN Patel RA Lavezzi W Gangloff SC Goyert SM Caimano MJ Radolf JD Sellati TJ 《Journal of immunology (Baltimore, Md. : 1950)》2005,174(3):1539-1548
Lyme disease is a chronic inflammatory disorder caused by the spirochetal bacterium, Borrelia burgdorferi. In vitro evidence suggests that binding of spirochetal lipoproteins to CD14, a pattern recognition receptor expressed on monocytes/macrophages and polymorphonuclear cells, is a critical requirement for cellular activation and the subsequent release of proinflammatory cytokines that most likely contribute to symptomatology and clinical manifestations. To test the validity of this notion, we assessed the impact of CD14 deficiency on Lyme disease in C3H/HeN mice. Contrary to an anticipated diminution in pathology, CD14(-/-) mice exhibited more severe and persistent inflammation than did CD14(+/+) mice. This disparity reflects altered gene regulation within immune cells that may engender the higher bacterial burden and serum cytokine levels observed in CD14(-/-) mice. Comparing their in vitro stimulatory activity, live spirochetes, but not lysed organisms, were a potent CD14-independent stimulus of cytokine production, triggering an exaggerated response by CD14(-/-) macrophages. Collectively, our in vivo and in vitro findings support the provocative notion that: 1) pattern recognition by CD14 is entirely dispensable for elaboration of an inflammatory response to B. burgdorferi, and 2) CD14-independent signaling pathways are inherently more destructive than CD14-dependent pathways. Continued study of CD14-independent signaling pathways may provide mechanistic insight into the inflammatory processes that underlie development of chronic inflammation. 相似文献
130.
Bhella D Goodfellow IG Roversi P Pettigrew D Chaudhry Y Evans DJ Lea SM 《The Journal of biological chemistry》2004,279(9):8325-8332
Echovirus type 12 (EV12), an Enterovirus of the Picornaviridae family, uses the complement regulator decay-accelerating factor (DAF, CD55) as a cellular receptor. We have calculated a three-dimensional reconstruction of EV12 bound to a fragment of DAF consisting of short consensus repeat domains 3 and 4 from cryo-negative stain electron microscopy data (EMD code 1057). This shows that, as for an earlier reconstruction of the related echovirus type 7 bound to DAF, attachment is not within the viral canyon but occurs close to the 2-fold symmetry axes. Despite this general similarity our reconstruction reveals a receptor interaction that is quite different from that observed for EV7. Fitting of the crystallographic co-ordinates for DAF(34) and EV11 into the reconstruction shows a close agreement between the crystal structure of the receptor fragment and the density for the virus-bound receptor, allowing unambiguous positioning of the receptor with respect to the virion (PDB code 1UPN). Our finding that the mode of virus-receptor interaction in EV12 is distinct from that seen for EV7 raises interesting questions regarding the evolution and biological significance of the DAF binding phenotype in these viruses. 相似文献