Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fluorescence-activated cell sorting was used to isolate 19 independent, temperature-sensitive, low density lipoprotein (LDL) receptor-deficient Chinese hamster ovary cell mutants that define three recessive complementation groups, ldlE, ldlF, ldlG. LDL receptor activity, essentially normal at the permissive temperature (34 degrees C), was virtually abolished in the mutants after incubation for 8-12 h at the nonpermissive temperature (39-40.5 degrees C). The mutants died after incubation for > 24 h at 39.5 degrees C. These mutants exhibited two striking and unexpected abnormalities that suggest that they define three genes important for general vesicular membrane traffic. First, LDL receptors were degraded abnormally rapidly at the nonpermissive temperature (chloroquine inhibited this degradation in ldlE and ldlG, but not in ldlF). In ldlE cells, the rapid degradation did not require efficient receptor clustering into coated pits and was not observed for all cell surface proteins. This selective degradation may be due to endocytic missorting. Second, the mutants exhibited temperature-sensitive defects in the posttranslational processing and intracellular transport of many membrane-associated and secreted proteins, including the LDL, mannose 6-phosphate/insulin-like growth factor II, and scavenger receptors, the vesicular stomatitis virus G protein and decay accelerating factor. Although the initial synthesis, folding, and processing of precursor forms of these proteins in the endoplasmic reticulum were apparently normal at the nonpermissive temperature, there was either a delay or a block in oligosaccharide processing associated with endoplasmic reticulum to medial Golgi transport at the nonpermissive temperature. This was accompanied by a dramatic inhibition of total soluble protein secretion. The posttranslational processing defects, the instability of cell surface LDL receptors, and the defective protein secretion exhibited by these mutants suggest that the ldlE-G gene products regulate or participate in reactions that are vital for a variety of secretory and endocytic membrane transport processes. This suggestion is strongly supported by our recent observation that a cDNA encoding a component of the coatomer, epsilon-COP, corrects the mutant phenotypes of ldlF cells (Guo, Q., Vasile, E., and Krieger, M. (1994) J. Cell Biol. 125, 1213-1224). Thus, these mutant cells should prove useful for further genetic and biochemical analysis of the mechanisms underlying intracellular membrane traffic.
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PMID:Isolation of three classes of conditional lethal Chinese hamster ovary cell mutants with temperature-dependent defects in low density lipoprotein receptor stability and intracellular membrane transport. 806 14

Recent evidence has suggested that subunits of the coatomer protein (COPI) complexes are functionally associated with endosomes in mammalian cells. We now provide genetic evidence that COPI plays a role in endocytosis in intact cells. The ldlF mutant CHO cell line bears a temperature-sensitive defect in the COPI subunit epsilon-COP. In addition to exhibiting conditional defects in the secretory pathway, we find that the cells are also defective at mediating endosome-associated functions. As found for cells microinjected with anti-COPI antibodies, ldlF cells at the restrictive temperature could not be infected by vesicular stomatitis (VSV) or Semliki Forest virus (SFV) that require delivery to acidic endosomes to penetrate into the cytosol. Although there was no temperature-sensitive defect in the internalization of receptor-bound transferrin (Tfn), Tfn recycling and accumulation of HRP were markedly inhibited at the restrictive temperature. Sorting of receptor-bound markers such as EGF to lysosomes was also reduced, although delivery of fluid-phase markers was only partially inhibited. In addition, lysosomes redistributed from their typical perinuclear location to the tips of the ldlF cells. Mutant phenotypes began to emerge within 2 h of temperature shift, the time required for the loss of detectable epsilon-COP, suggesting that the endocytic defects were not secondary to a block in the secretory pathway. Importantly, the mutant phenotypes were also corrected by transfection of wild-type epsilon-COP cDNA demonstrating that they directly or indirectly reflected the epsilon-COP defect. Taken together, the results suggest that epsilon-COP acts early in the endocytic pathway, most likely inhibiting the normal sorting and recycling functions of early endosomes.
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PMID:Inhibition of endosome function in CHO cells bearing a temperature-sensitive defect in the coatomer (COPI) component epsilon-COP. 941 69