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601.
F Revah D Bertrand J L Galzi A Devillers-Thiéry C Mulle N Hussy S Bertrand M Ballivet J P Changeux 《Nature》1991,353(6347):846-849
A variety of ligand-gated ion channels undergo a fast activation process after the rapid application of agonist and also a slower transition towards desensitized or inactivated closed channel states when exposure to agonist is prolonged. Desensitization involves at least two distinct closed states in the acetylcholine receptor, each with an affinity for agonists higher than those of the resting or active conformations. Here we investigate how structural elements could be involved in the desensitization of the acetylcholine-gated ion channel from the chick brain alpha-bungarotoxin sensitive homo-oligomeric alpha 7 receptor, using site-directed mutagenesis and expression in Xenopus oocytes. Mutations of the highly conserved leucine 247 residue from the uncharged MII segment of alpha 7 suppress inhibition by the open-channel blocker QX-222, indicating that this residue, like others from MII, faces the lumen of the channel. But, unexpectedly, the same mutations decrease the rate of desensitization of the response, increase the apparent affinity for acetylcholine and abolish current rectification. Moreover, unlike wild-type alpha 7, which has channels with a single conductance level, the leucine-to-threonine mutant has an additional conducting state active at low acetylcholine concentrations. It is possible that mutation of Leu 247 renders conductive one of the high-affinity desensitized states of the receptor. 相似文献
602.
A three-base-pair deletion in the peripherin-RDS gene in one form of retinitis pigmentosa. 总被引:59,自引:0,他引:59
G J Farrar P Kenna S A Jordan R Kumar-Singh M M Humphries E M Sharp D M Sheils P Humphries 《Nature》1991,354(6353):478-480
The group of retinopathies termed retinitis pigmentosa (RP) greatly contribute to visual dysfunction in man with a frequency of roughly 1 in 4,000. We mapped the first autosomal dominant RP (adRP) gene to chromosome 3q, close to the gene encoding rhodopsin, a rod photoreceptor pigment protein. Subsequently, mutations in this gene have been implicated as responsible for some forms of adRP. Another adRP gene has been mapped to chromosome 8p. A third adRP gene in a large Irish pedigree has been mapped to chromosome 6p, showing tight linkage with the gene for peripherin, a photoreceptor cell-specific glycoprotein, which is thus a strong candidate for the defective gene. We have now identified a three-base-pair deletion which results in the loss of one of a pair of highly conserved cysteine residues in the predicted third transmembrane domain of peripherin. This deletion segregates with the disease phenotype but is not present in unaffected controls, and suggests that mutant peripherin gives rise to retinitis pigmentosa. 相似文献
603.
High-affinity NGF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor. 总被引:90,自引:0,他引:90
Nerve growth factor (NGF) interacts with two different low-affinity receptors that can be distinguished by affinity crosslinking. Reconstitution experiments by membrane fusion and transient transfection into heterologous cells indicate that high-affinity NGF binding requires coexpression and binding to both the low-affinity NGF receptor and the tyrosine kinase trk gene product. These studies reveal a new growth factor receptor-mediated mechanism of cellular differentiation involving trk and the low-affinity NGF receptor. 相似文献
604.
605.
Running energetics in the pronghorn antelope 总被引:1,自引:0,他引:1
The pronghorn antelope (Antilocapra americana) has an alleged top speed of 100 km h-1, second only to the cheetah (Acionyx jubatus) among land vertebrates, a possible response to predation in the exposed habitat of the North American prairie. Unlike cheetahs, however, pronghorn antelope are distance runners rather than sprinters, and can run 11 km in 10 min, an average speed of 65 km h-1. We measured maximum oxygen uptake in pronghorn antelope to distinguish between two potential explanations for this ability: either they have evolved a uniquely high muscular efficiency (low cost of transport) or they can supply oxygen to the muscles at unusually high levels. Because the cost of transport (energy per unit distance covered per unit body mass) varies as a predictable function of body mass among terrestrial vertebrates, we can calculate the predicted cost to maintain speeds of 65 and 100 km h-1 in an average 32-kg animal. The resulting range of predicted values, 3.2-5.1 ml O2 kg-1 s-1, far surpasses the predicted maximum aerobic capacity of a 32-kg mammal (1.5 ml O2 kg-1 s-1). We conclude that their performance is achieved by an extraordinary capacity to consume and process enough oxygen to support a predicted running speed greater than 20 ms-1 (70 km h-1), attained without unique respiratory-system structures. 相似文献
606.
A coat subunit of Golgi-derived non-clathrin-coated vesicles with homology to the clathrin-coated vesicle coat protein beta-adaptin 总被引:76,自引:0,他引:76
T Serafini G Stenbeck A Brecht F Lottspeich L Orci J E Rothman F T Wieland 《Nature》1991,349(6306):215-220
Four high-molecular-weight proteins form the main subunits of the coat of Golgi-derived (non-clathrin) coated vesicles. One of these coat proteins, beta-COP, is identical to a Golgi-associated protein of relative mass 110,000 (110K) that shares homology with the adaptin proteins of clathrin-coated vesicles. This connection, and the comparable molecular weights of the coat proteins of Golgi-derived and clathrin-coated vesicles, indicates that they may be structurally related. The identification of beta-COP as the 110K protein explains the blocking of secretion by the drug brefeldin A. 相似文献
607.
New use of BCG for recombinant vaccines 总被引:147,自引:0,他引:147
C K Stover V F de la Cruz T R Fuerst J E Burlein L A Benson L T Bennett G P Bansal J F Young M H Lee G F Hatfull 《Nature》1991,351(6326):456-460
BCG, a live attenuated tubercle bacillus, is the most widely used vaccine in the world and is also a useful vaccine vehicle for delivering protective antigens of multiple pathogens. Extrachromosomal and integrative expression vectors carrying the regulatory sequences for major BCG heat-shock proteins have been developed to allow expression of foreign antigens in BCG. These recombinant BCG strains can elicit long-lasting humoral and cellular immune responses to foreign antigens in mice. 相似文献
608.
Complex patterns formed by motile cells of Escherichia coli 总被引:6,自引:0,他引:6
When chemotactic strains of the bacterium Escherichia coli are inoculated on semi-solid agar containing mixtures of amino acids or sugars, the cells swarm outwards in a series of concentric rings: they respond to spatial gradients of attractants generated by uptake and catabolism. Cells also drift up gradients generated artificially, for example by diffusion from the tip of a capillary tube or by mixing. Here we describe conditions under which cells aggregate in response to gradients of attractant which they excrete themselves. When cells are grown in semi-solid agar on intermediates of the tricarboxylic acid cycle, they form symmetrical arrays of spots or stripes that arise sequentially. When cells in a thin layer of liquid culture are exposed to these compounds, spots appear synchronously, more randomly arrayed. In either case, the patterns are stationary. The attractant is a chemical sensed by the aspartate receptor. Its excretion can be triggered by oxidative stress. As oxygen is limiting at high cell densities, aggregation might serve as a mechanism for collective defence. 相似文献
609.
Enhancement of T-cell activation by the CD43 molecule whose expression is defective in Wiskott-Aldrich syndrome 总被引:9,自引:0,他引:9
J K Park Y J Rosenstein E Remold-O'Donnell B E Bierer F S Rosen S J Burakoff 《Nature》1991,350(6320):706-709
CD43 (sialophorin, leukosialin, leukocyte large sialoglycoprotein), a heavily sialylated molecule found on most leukocytes and platelets, was initially identified as a major glycoprotein of mouse, rat and human T cells. CD43 expression is defective on the T cells of males with the Wiskott-Aldrich syndrome, an X chromosome-linked recessive immunodeficiency disorder. Affected males are susceptible to opportunistic infections and do not respond to polysaccharide antigens, reflecting defects in cytotoxic and helper T-cell functions. Anti-CD43 monoclonal antibodies have a modest costimulatory effect on T cells, natural killer cells, B cells and monocytes, and one such antibody has been shown to activate T cells directly. To investigate a possible physiological role for CD43, a complementary DNA encoding the human protein was introduced into an antigen-responsive murine T-cell hybridoma. We observed that CD43 enhances the antigen-specific activation of T cells and that the intracellular domain of CD43, which is hyperphosphorylated during T-cell activation, is required for this function. We also found that antigen-presenting cells can bind specifically to immobilized purified CD43 and that the binding can be inhibited by liposomes containing CD43 as well as by anti-CD43 monoclonal antibodies. 相似文献
610.
Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1 总被引:135,自引:0,他引:135
L Pevny M C Simon E Robertson W H Klein S F Tsai V D'Agati S H Orkin F Costantini 《Nature》1991,349(6306):257-260