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101.
Cellular membranes contain many types and species of lipids. One of the most important functional consequences of this heterogeneity is the existence of microdomains within the plane of the membrane. Sphingolipid acyl chains have the ability of forming tightly packed platforms together with sterols. These platforms or lipid rafts constitute segregation and sorting devices into which proteins specifically associate. In budding yeast, Saccharomyces cerevisiae, lipid rafts serve as sorting platforms for proteins destined to the cell surface. The segregation capacity of rafts also provides the basis for the polarization of proteins at the cell surface during mating. Here we discuss some recent findings that stress the role of lipid rafts as key players in yeast protein sorting and cell polarity. 相似文献
102.
Conflicting reports exist regarding the ability of quinine to activate neurons in the trigeminal system. We used the complementary approaches of single-unit electrophysiology and c-fos immunohistochemistry to investigate whether quinine (100 mM) activates chemonociceptive cells in the brainstem trigeminal subnucleus caudalis (Vc). In electrophysiological experiments, 38 units responded to noxious mechanical, thermal and chemical (200 mM pentanoic acid) stimuli applied to the tongue with an increase in firing rate; none responded to lingual quinine whether the quinine was presented before or after application of pentanoic acid. In the c-fos immunohistochemical experiment, both quinine and water elicited equivalent levels of fos-like immunoreactivity (FLI) in dorsomedial Vc that were significantly lower than the level of FLI evoked by pentanoic acid. These data collectively indicate that quinine does not elicit activity in chemonociceptive Vc neurons. 相似文献
103.
A note: ortho-phthalaldehyde: proposed mechanism of action of a new antimicrobial agent 总被引:4,自引:0,他引:4
Ortho-phthalaldehyde (OPA) is a new aromatic dialdehyde antimicrobial agent, the mechanism of action of which has been little studied. The aims of this paper are to examine what is currently known about its mechanism of action, to compare the action with that of a widely investigated aliphatic dialdehyde, glutaraldehyde (GTA), and to put forward a hypothesis that would, in the light of current knowledge, explain how OPA inactivates micro-organisms, including GTA-resistant Mycobacterium chelonae. 相似文献
104.
105.
Sphingolipid-cholesterol rafts diffuse as small entities in the plasma membrane of mammalian cells 总被引:1,自引:0,他引:1
To probe the dynamics and size of lipid rafts in the membrane of living cells, the local diffusion of single membrane proteins was measured. A laser trap was used to confine the motion of a bead bound to a raft protein to a small area (diam < or = 100 nm) and to measure its local diffusion by high resolution single particle tracking. Using protein constructs with identical ectodomains and different membrane regions and vice versa, we demonstrate that this method provides the viscous damping of the membrane domain in the lipid bilayer. When glycosylphosphatidylinositol (GPI) -anchored and transmembrane proteins are raft-associated, their diffusion becomes independent of the type of membrane anchor and is significantly reduced compared with that of nonraft transmembrane proteins. Cholesterol depletion accelerates the diffusion of raft-associated proteins for transmembrane raft proteins to the level of transmembrane nonraft proteins and for GPI-anchored proteins even further. Raft-associated GPI-anchored proteins were never observed to dissociate from the raft within the measurement intervals of up to 10 min. The measurements agree with lipid rafts being cholesterol-stabilized complexes of 26 +/- 13 nm in size diffusing as one entity for minutes. 相似文献
106.
Simons M 《Nature medicine》2000,6(9):965-966
107.
Lipid Domain Structure of the Plasma Membrane Revealed by Patching of Membrane Components 总被引:32,自引:0,他引:32 下载免费PDF全文
Thomas Harder Peter Scheiffele Paul Verkade Kai Simons 《The Journal of cell biology》1998,141(4):929-942
Lateral assemblies of glycolipids and cholesterol, “rafts,” have been implicated to play a role in cellular processes like membrane sorting, signal transduction, and cell adhesion. We studied the structure of raft domains in the plasma membrane of non-polarized cells. Overexpressed plasma membrane markers were evenly distributed in the plasma membrane. We compared the patching behavior of pairs of raft markers (defined by insolubility in Triton X-100) with pairs of raft/non-raft markers. For this purpose we cross-linked glycosyl-phosphatidylinositol (GPI)-anchored proteins placental alkaline phosphatase (PLAP), Thy-1, influenza virus hemagglutinin (HA), and the raft lipid ganglioside GM1 using antibodies and/or cholera toxin. The patches of these raft markers overlapped extensively in BHK cells as well as in Jurkat T–lymphoma cells. Importantly, patches of GPI-anchored PLAP accumulated src-like protein tyrosine kinase fyn, which is thought to be anchored in the cytoplasmic leaflet of raft domains. In contrast patched raft components and patches of transferrin receptor as a non-raft marker were sharply separated. Taken together, our data strongly suggest that coalescence of cross-linked raft elements is mediated by their common lipid environments, whereas separation of raft and non-raft patches is caused by the immiscibility of different lipid phases. This view is supported by the finding that cholesterol depletion abrogated segregation. Our results are consistent with the view that raft domains in the plasma membrane of non-polarized cells are normally small and highly dispersed but that raft size can be modulated by oligomerization of raft components. 相似文献
108.
Cell wall 1,6-beta-glucan synthesis in Saccharomyces cerevisiae depends on ER glucosidases I and II, and the molecular chaperone BiP/Kar2p. 总被引:1,自引:1,他引:0 下载免费PDF全文
The role of glucose trimming in the endoplasmic reticulum of Saccharomyces cerevisiae was investigated using glucosidase inhibitors and mutant strains devoid of glucosidases I and II. These glucosidases are responsible for removing glucose residues from the N-linked core oligosaccharides attached to newly synthesized polypeptide chains. In mammalian cells they participate together with calnexin, calreticulin and UDP-glucose:glycoprotein glucosyltransferase in the folding and quality control of newly synthesized glycoproteins. In S.cerevisiae, glucosidase II is encoded by the GLS2 gene, and glucosidase I, as suggested here, by the CWH41 gene. Using castanospermine (an alpha-glucosidase inhibitor) and yeast strains defective in glucosidase I, glucosidase II and BiP/Kar2p, it was demonstrated that cell wall synthesis depends on the two glucosidases and BiP/Kar2p. In double mutants with defects in both BiP/Kar2p and either of the glucosidases the phenotype was particularly clear: synthesis of 1,6-beta-glucan_a cell wall component_was reduced; the cell wall displayed abnormal morphology; the cells aggregated; and their growth was severely inhibited. No defects in protein folding or secretion could be detected. We concluded that glucose trimming in S.cerevisiae is necessary for proper cell wall synthesis, and that the glucosidases function synergistically with BiP/Kar2p in this process. 相似文献
109.
Disinfectant testing: use of the Bioscreen Microbiological Growth Analyser for laboratory biocide screening 总被引:5,自引:0,他引:5
A new method is described for screening potential biocides based on the traditional suspension test using the Bioscreen optical plate reader. This new method is rapid, reproducible, quantitative and cost effective. Data obtained by this new method are not directly equivalent to the log reduction normally quoted, but give a measurement of the total effect of the biocide on the microbe population, measuring the effect of injury as well as death (non-viability). The method allows for the routine examination of disinfection kinetics, the study of which leads to greater scientific insight into disinfection than that achieved by the standard 5 min, one-point, disinfection tests currently employed. 相似文献
110.
Saara Laulumaa Tuomo Nieminen Mari Lehtim?ki Shweta Aggarwal Mikael Simons Michael M. Koza Ilpo Vattulainen Petri Kursula Francesca Natali 《PloS one》2015,10(6)
Myelin protein P2 is a fatty acid-binding structural component of the myelin sheath in the peripheral nervous system, and its function is related to its membrane binding capacity. Here, the link between P2 protein dynamics and structure and function was studied using elastic incoherent neutron scattering (EINS). The P38G mutation, at the hinge between the β barrel and the α-helical lid, increased the lipid stacking capacity of human P2 in vitro, and the mutated protein was also functional in cultured cells. The P38G mutation did not change the overall structure of the protein. For a deeper insight into P2 structure-function relationships, information on protein dynamics in the 10 ps to 1 ns time scale was obtained using EINS. Values of mean square displacements mainly from protein H atoms were extracted for wild-type P2 and the P38G mutant and compared. Our results show that at physiological temperatures, the P38G mutant is more dynamic than the wild-type P2 protein, especially on a slow 1-ns time scale. Molecular dynamics simulations confirmed the enhanced dynamics of the mutant variant, especially within the portal region in the presence of bound fatty acid. The increased softness of the hinge mutant of human myelin P2 protein is likely related to an enhanced flexibility of the portal region of this fatty acid-binding protein, as well as to its interactions with the lipid bilayer surface requiring conformational adaptations. 相似文献