Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polyethylene glycols (PEG) with molecular weight less than or equal to 3000 were shown to effectively protect human erythrocytes from osmotic lysis induced by alpha-staphylotoxin (ST). PEG with MW less than 3000 do not change the conductivity of ion channels induced by ST in bilayer lipid membranes (BLM). Changing the bilayer from a pure phosphatidylcholine (PC) to a negatively charged phosphatidylserine (PS) film results in an asymmetry of the current-voltage characteristics. This is evidenced by the asymmetrical position of the ST-channel pore in bilayer membranes. The results obtained allow to conclude that the ST-channel is an interprotein pore filled with water (with an inner diameter of 2.5-3 nm and a length of approximately 10 nm). It is composed of six molecules of alpha-toxin from Staphylococcus aureus. The ST-channel incorporates into a membrane with only one mouth in contact with the polar lipid heads and the other one protruding 4.5-5 nm from the bilayer plane in water solution.
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PMID:The structure of Staphylococcus aureus alpha-toxin-induced ionic channel. 246 32

The purpose of this investigation was to study the effects of a distinct type of phospholipase C on sarcolemmal Na+-Ca2+ exchange. With this phospholipase C (Staphylococcus aureus), treatment of cardiac sarcolemmal vesicles resulted in a specific hydrolysis of membrane phosphatidylinositol. This hydrolysis of phosphatidylinositol also released two proteins (110 and 36 kDa) from the sarcolemmal membrane. Phospholipase C pretreatment of the sarcolemma resulted in an unexpected stimulation of Na+-Ca2+ exchange. The Vmax of Na+-Ca2+ exchange was increased but the Km for Ca2+ was not altered. This stimulation was specific to the Na+-Ca2+ exchange pathway. ATP-dependent Ca2+ uptake was depressed after phospholipase C treatment, but passive membrane permeability to Ca2+ was unaffected. Sarcolemmal Na+,K+-ATPase activity was not altered, whereas passive Ca2+ binding was modestly decreased after phospholipase C pretreatment. The stimulation of Na+-Ca2+ exchange after phosphatidylinositol hydrolysis was greater in inside-out vesicles than in a total population of vesicles of mixed orientation. This finding suggests that the cardiac sarcolemmal Na+-Ca2+ exchanger is functionally asymmetrical. The results also suggest that membrane phosphatidylinositol is inhibitory to the Na+-Ca2+ exchanger or, alternatively, this phospholipid may anchor an endogenous inhibitory protein in the sarcolemmal membrane. The observation that a transsarcolemmal Ca2+ flux pathway may be stimulated solely by phosphatidylinositol hydrolysis independently of phosphoinositide metabolic products like inositol triphosphate is novel.
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PMID:Role of phosphatidylinositol in cardiac sarcolemmal membrane sodium-calcium exchange. 254 59

The distribution of the three major phospholipids of bovine rod outer segment disk membranes over the two faces of the membrane has been studied by means of treatment with phospholipase C, phospholipase A2 and phospholipase D. Two different preparations of rod outer segment disk membranes have been used, which are called 'stacked disks' and 'disk vesicles' on account of their morphological appearance. The hydrolysis patterns obtained by phospholipase treatment of these preparations have been compared to those of a retinal lipid suspension or detergent-solubilized disk membranes, which serve as control preparations with a similar phospholipid composition but a random availability of the phospholipids. Special attention is given to the early phase of enzyme treatment in order to eliminate secondary effects on the molecular organization of the membrane due to appreciable phospholipid hydrolysis. Analysis of the hydrolysis patterns for all three phospholipases in stacked disks, as compared to those in randomized control preparations, suggests a slightly asymmetrical distribution of phosphatidylcholine (40--45% at the outer face) and phosphatidylethanolamine (55--60% at the outer face) and a symmetrical distribution of phosphatidylserine in rod outer segment disk membranes. Extensive treatment with phospholipases C and A2 leads ultimately to nearly complete hydrolysis of all phospholipids, but with phospholipase D a final level of 40% phospholipid hydrolysis is observed in stacked disk preparations. This suggests that in the latter case the inner face of the membrane is inaccessible to the enzyme. Further work will be necessary in order to substantiate these conclusions.
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PMID:Transbilayer distribution of phospholipids in photoreceptor membrane studied with various phospholipases. 744 82

The distribution of phosphatidylethanolamine (PE) and phosphatidylcholine (PC) among the outer and inner monolayers of the vacuolar membrane of Acer pseudoplatanus was investigated using isolated vacuoles, chemical labelling agents (trinitrobenzene-sulfonate and fluorescamine), phospholipase A2 from bee venom, phospholipase C and phospholipase D. Treatments were performed with intact or sonicated vacuoles. Analysis of the transbilayer distribution of PC and PE in the vacuolar membrane of Acer was limited by phospholipid fractions which were inaccessible to the probes. Lipid-protein interactions and modification of the surface charge and surface pressure in the membrane layers during treatments may obviously exert a strong influence on labelling or hydrolysis of membrane phospholipids. However, simultaneous treatments carried out with phospholipase A2 and phospholipase C show that PE is approximately 20% more abundant in the outer monolayer than in the inner monolayer and PC is equally distributed between both leaflets of tonoplast. Compared to the phospholipids asymmetrical distribution observed in plasma membrane of erythrocyte, the vacuolar membrane of Acer is not characterized by a marked asymmetrical distribution of its major phospholipids.
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PMID:Transbilayer distribution of phosphatidylcholine and phosphatidylethanolamine in the vacuolar membrane of Acer pseudoplatanus cells. 764 9

Asymmetrical (one-sided) application of penetrating water-soluble polymers, polyethylene glycols (PEGs), to a well-defined channel formed by Staphylococcus aureus alpha-toxin is shown to probe channel pore geometry in more detail than their symmetrical (two-sided) application. Polymers added to the cis side of the planar lipid membrane (the side of protein addition) affect channel conductance differently than polymers added to the trans side. Because a satisfactory theory quantitatively describing PEG partitioning into a channel pore does not exist, we apply the simple empirical rules proposed previously (, J. Membr. Biol. 161:83-92) to gauge the size of pore openings as well as the size and position of constrictions along the pore axis. We estimate the radii of the two openings of the channel to be practically identical and equal to 1. 2-1.3 nm. Two apparent constrictions with radii of approximately 0. 9 nm and approximately 0.6-0.7 nm are inferred to be present in the channel lumen, the larger one being closer to the cis side. These structural findings agree well with crystallographic data on the channel structure (, Science. 274:1859-1866) and verify the practicality of polymer probing. The general features of PEG partitioning are examined using available theoretical considerations, assuming there is no attraction between PEG and the channel lumen. It is shown that the sharp dependence of the partition coefficient on polymer molecular weight found under both symmetrical and asymmetrical polymer application can be rationalized within a "hard sphere nonideal solution model." This finding is rather surprising because PEG forms highly flexible coils in water with a Kuhn length of only several Angstroms.
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PMID:Polymeric nonelectrolytes to probe pore geometry: application to the alpha-toxin transmembrane channel. 1058 24

Upon activation of receptors coupled to the Gq subclass of G proteins, phospholipase C (PLC)beta hydrolyses membrane phospholipid to yield a pair of second messengers, inositol 1,4,5-trisphosphate and 1,2-diacylglycerol. Of four PLCbeta isoforms, PLCbeta1 is transcribed predominantly in the telencephalon and its gene inactivation in mice impairs metabotropic glutamate receptor- and muscarinic acetylcholine receptor-dependent hippocampal oscillations, endocannabinoid production in the hippocampus and barrel formation in the somatosensory cortex. Here we examined cellular and subcellular distributions of PLCbeta1 in adult mouse brains. In the telencephalon, high levels of PLCbeta1 were observed in principal neurons, including pyramidal cells in the cortex and hippocampus, granule cells and mossy cells in the dentate gyrus, and medium spiny neurons in the caudate-putamen, whereas most interneurons had low levels of or were negative for PLCbeta1 and, instead, expressed PLCbeta4. By immunofluorescence, tiny clusters of PLCbeta1 were distributed in somatodendritic compartments of principal neurons and positioned close to those of metabotropic glutamate receptor 5, muscarinic acetylcholine receptor M1 and diacylglycerol lipase-alpha, respectively. Immunoelectron microscopy revealed that PLCbeta1 was often associated with the smooth endoplasmic reticulum, cell membrane or postsynaptic density. In particular, it was highly accumulated at the perisynapse of dendritic spines forming asymmetrical synapses. In the cerebellum, PLCbeta1 was generally low but was enriched in axons and dendrites of basket cells. These results suggest that PLCbeta1 is the key effector in telencephalic principal neurons and cerebellar interneurons. Furthermore, the well-orchestrated molecular arrangement appears to be the anatomical basis for the specificity, efficiency and convergence of the neuronal phosphoinositide signaling system.
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PMID:Predominant expression of phospholipase Cbeta1 in telencephalic principal neurons and cerebellar interneurons, and its close association with related signaling molecules in somatodendritic neuronal elements. 1897 90

Following activation of Gq protein-coupled receptors, phospholipase C yields a pair of second messengers, i.e. diacylglycerol (DAG) and inositol 1,4,5-trisphosphate. The former activates protein kinase C and the latter mobilizes Ca(2+) from intracellular store. DAG kinase (DGK) then phosphorylates DAG to produce another second messenger (phosphatidic acid). Of 10 mammalian DGK isozymes, DGKbeta is expressed in dopaminergic projection fields with the highest level in the striatum and its particular splice variant is differentially expressed in patients with bipolar disorder. To gain molecular anatomical evidence for its signaling role, we investigated the cellular expression and subcellular localization of DGKbeta in the striatum of rat brain. DGKbeta was expressed in medium spiny neurons constituting the striatonigral and striatopallidal pathways, whereas striatal interneurons were below the detection threshold. DGKbeta was distributed in somatodendritic elements of medium spiny neurons and localized in association with the smooth endoplasmic reticulum and plasma membrane or in the narrow cytoplasmic space between them. In particular, DGKbeta exhibited dense accumulation at perisynaptic sites on dendritic spines forming asymmetrical synapses. The characteristic anatomical localization was consistent with exclusive enrichment of DGKbeta in the microsomal and postsynaptic density fractions. Intriguingly, DGKbeta was very similar in immunohistochemical and immunochemical distribution to Gq-coupled receptors, such as metabotropic glutamate receptors 1 and 5, and also to other downstream molecules involving DAG metabolism, such as phospholipase C beta and DAG lipase. These findings suggest that abundant DGKbeta is provided to perisynaptic sites of medium spiny neurons so that it can effectively produce phosphatidic acid upon activation of Gq-coupled receptors and modulate the cellular state of striatal output neurons.
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PMID:Diacylglycerol kinase beta accumulates on the perisynaptic site of medium spiny neurons in the striatum. 1908 71

The asymmetrical distribution of F-actin directed by cell polarity has been observed during the migration of monospores from the red alga Porphyra yezoensis. The significance of Ca2+ influx and phosphoinositide signalling during the formation of cell polarity in migrating monospores was analysed pharmacologically. The results indicate that the inhibition of the establishment of cell polarity, as judged by the ability of F-actin to localize asymmetrically, cell wall synthesis, and development into germlings, occurred when monospores were treated with inhibitors of the Ca2+ permeable channel, phospholipase C (PLC), diacylglycerol kinase, and inositol-1,4,5-trisphosphate receptor. Moreover, it was also found that light triggered the establishment of cell polarity via photosynthetic activity but not its direction, indicating that the Ca2+ influx and PLC activation required for the establishment of cell polarity are light dependent. By contrast, inhibition of phospholipase D (PLD) prevented the migration of monospores but not the asymmetrical localization of F-actin. Taken together, these findings suggest that there is functional diversity between the PLC and PLD signalling systems in terms of the formation of cell polarity; the former being critical for the light-dependent establishment of cell polarity and the latter playing a role in the maintenance of established cell polarity.
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PMID:Ca2+ influx and phosphoinositide signalling are essential for the establishment and maintenance of cell polarity in monospores from the red alga Porphyra yezoensis. 1993 78

Unicellular spore cells, designated as monospores (also called archeospores), are well known as migrating plant cells, in which establishment of the anterior-posterior axis directs asymmetrical distribution of F-actin. Since the mechanisms of cell polarity formation are not yet fully elucidated in monospores, we investigated the roles of phosphoinositide signaling systems and Ca2+ mobilization in migration. Although we have already found the critical involvement of phosphatidylinositol 3-kinase in the establishment of cell polarity, we recently demonstrated the important roles of extracellular Ca2+ influx, phospholipase C (PLC) and phospholipase D (PLD). The remarkable characteristics of these factors are that Ca2+ influx depends on photosynthetic activity and that PLC and PLD play roles in the establishment and maintenance of cell polarity, respectively. These findings could provide new insight into the regulation of migration in eukaryotic cells.
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PMID:Photosynthesis-dependent Ca2+ influx and functional diversity between phospholipases in the formation of cell polarity in migrating cells of red algae. 1953 46