Aspects Of Membrane Function Research Articles

Lipid-Assisted Membrane Protein Folding and Topogenesis.

Due to the heterogenous lipid environment in which integral membrane proteins are embedded, they should follow a set of assembly rules, which govern transmembrane protein folding and topogenesis accordingly to a given lipid profile. Recombinant strains of bacteria have been engineered to have different membrane phospholipid compositions by molecular genetic manipulation of endogenous and foreign genes encoding lipid biosynthetic enzymes. Such strains provide a means to investigate the in vivo role of lipids in many different aspects of membrane function, folding and biogenesis. In vitro and in vivo studies established a function of lipids as molecular chaperones and topological determinants specifically assisting folding and topogenesis of membrane proteins. These results led to the extension of the Positive Inside Rule to Charge Balance Rule, which incorporates a role for lipid-protein interactions in determining membrane protein topological organization at the time of initial membrane insertion and dynamically after initial assembly. Membrane protein topogenesis appears to be a thermodynamically driven process in which lipid-protein interactions affect the potency of charged amino acid residues as topological signals. Dual topology for a membrane protein can be established during initial assembly where folding intermediates in multiple topological conformations are in rapid equilibrium (thus separated by a low activation energy), which is determined by the lipid environment. Post-assembly changes in lipid composition or post-translational modifications can trigger a reorganization of protein topology by inducing destabilization and refolding of a membrane protein. The lipid-dependent dynamic nature of membrane protein organization provides a novel means of regulating protein function.

人工膜と生体膜の接点を探る―膜構造と機能発現 脂質の物性から見た生体膜の構造形成と機能

The interactions of membrane proteins with lipid bilayers are principally hydrophobic and electrostatic in nature. Integral proteins interact hydrophobically with the hydrocarbon chains of membrane lipids by crossing the bilayer once or several times. Since every biomembrane contains a wide variety of different lipid species, an understanding of the differential interactions between proteins and lipids is required to clarify many aspects of membrane functions. The integral membrane proteins have an amphipathic nature since there exist separated surfaces of hydrophobic and hydrophilic regions. The hydrophobic force is the major factor in constructing the biomembrane structures, and so the hydrophobic part of integral protein traverses or penetrates the hydrophobic core of the lipid bilayer. In this review, matching of the hydrophobic regions of the lipids and proteins in membranes is discussed, and then a possible mechanism of activating protein kinase C in signal transduction of phosphatidylinositol cycle.

Biotechnological Aspects of Membrane Function

An overview is given of the biotechnological utilizability of various features of cell membranes. Techniques are given that describe how to make use of the barrier and transport functions of membranes for biotechnological purposes, ranging from cell permeabilization and construction of immobilized biocatalysts to manipulating excretion and uptake properties of the membranes by various methods. Glucose transporters, iron-transporting membrane systems, and pumps engaged in pleiotropic drug resistance are treated in more detail as particularly biotechnologically important membrane proteins.

Elevated Platelet Calcium Mobilization and Nitric Oxide Synthase Activity May Reflect Abnormalities in Schizophrenic Brain

Schizophrenia has a diverse nature of clinical symptoms and a number of hypotheses have been suggested to explain its aetiological basis. In this study we have examined two aspects of membrane function, receptor-activated calcium mobilization and calcium activated nitric oxide synthase activity in schizophrenic subjects. Thrombin induces mobilization of calcium ions from intracellular stores. The platelet response of drug naive schizophrenics was found to be significantly increased over a range of thrombin concentrations (0.01 to 0.60 U/ml) compared to control subjects. Possible involvement of nitric oxide (NO) in the aetiology of schizophrenia was investigated. NO has been functionally linked to both dopaminergic and glutamatergic systems both of which are strongly implicated in the biochemical pathology of schizophrenia. Nitric oxide synthase (NOS) activity was determined in platelets of controls, schizophrenic and panic disorder subjects. Enzyme activity was found to be significantly higher in platelets of drug naive schizophrenic subjects compared to controls, drug treated schizophrenics and panic disorder subjects. It is suggested that there is an imbalance of the calcium-induced L-arginine- nitric oxide pathway in platelets of schizophrenic subjects which may be modified by neuroleptic treatment. This imbalance may be mirrored in the central nervous system in particular at the NMDA receptor. It is possible that such a disturbance in the L-arginine-nitric oxide pathway may have pathological implications in the aetiology of schizophrenia.

Liposomes Recognized as Osmometers

Already in a very early stage of liposome research Alec Bangham transmitted his enthusiasm for phospholipid liquid crystals to the Centre of Biomembranes and Lipid Enzymology founded by Laurens van Deenen in Utrecht. As part of the friendly relationships that developed between the two laboratories I was a guest in the Babraham Institute in 1966 and in a joint approach we studied swelling properties of phospholipid dispersions in different salt solutions. By centrifugation of the dispersions and pellet measurements after equilibration at various osmotic concentrations we demonstrated that liposomes prepared of egg lecithin behave as practical ideal osmometers obeying the Boyle-van’t Hoff law (1). The result proved the existence of closed membrane vesicles bounded by lipid bilayers, permeable to water but impermeable to ions. Furthermore it indicated the usefulness of liposomes as membrane model systems. application as such introduced us into various fascinating aspects of membrane functions and it is a pleasure to give a very brief review of some findings concerning the barrier properties of membrane lipids. Taking advantage of changes in light scattering, osmotic volume changes of the liposomes could be followed in time. by comparison of pellet volumes and turbidities of dispersion after osmotic equilibration at various salt concentrations it appeared that there is a linear relationship between the pellet volume and the reverse of the optical extinction.

Increased content of a minor ankyrin in erythrocyte membranes of bipolar subjects

This preliminary study reports on the increased content of a structurally important protein in erythrocyte membranes of bipolar patients treated with lithium carbonate compared with control subjects. The external portion of the erythrocyte membrane is a lipid bilayer into which various integral proteins are inserted; some of these serve as ion channels or energy-dependent transport systems. Another group of proteins, including those termed “ankyrins,” link the bilayer to an underlying network of cytoskeletal proteins, and maintain both cell shape and the arrangement of integral proteins within the bilayer. Structural changes resulting from the observed excess of one of the ankyrins in membranes from bipolar subjects could alter several aspects of membrane function. Ankyrins also occur in neurons, where a corresponding increase would alter central nervous system function.

Introductory remarks

The purpose of this discussion meeting was to consider in depth the structures of some selected biological membranes and envelopes - in particular, those with marked, morphological substructure. Where such substructure could be related to function, this also was considered, the aim being to illustrate by multidisciplinary techniques the interdependence of membrane morphology and physiology. Inevitably, as the discussion was restricted to two days, with such a ubiquitous and pantomorphic subject as biological membranes, the field had to be strictly limited. Some of the most important aspects of membrane function, including bioenergetics, transport mechanisms and membrane flow, were deliberately excluded, largely because they have been the subjects of recent discussion meetings either at the Royal Society or elsewhere. Despite such restrictions, we had a distinguished field of research workers from whom to select our speakers. We were indeed fortunate, that so many were able to come, from many parts of the world, and contribute to this meeting.