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American Journal of Physiology. Renal... Dec 2000Embryonic epithelial membrane transporters are organized into transporter families that are functional in several epithelial organs, namely, in kidney, lung, pancreas,... (Review)
Review
Embryonic epithelial membrane transporters are organized into transporter families that are functional in several epithelial organs, namely, in kidney, lung, pancreas, intestine, and salivary gland. Family members (subtypes) are developmentally expressed in plasma membranes in temporospatial patterns that are 1) similar for one subtype within different organs, like aquaporin-1 (AQP1) in lung and kidney; 2) different between subtypes within the same organ, like the amiloride-sensitive epithelial sodium channel (ENaC) in lung; and 3) apparently matched among members of different transporter families, as alpha-ENaC with AQP1 and -4 in lung and with AQP2 in kidney. Finally, comparison of temporal expression patterns in early embryonic development of transporters from different families [e.g., cystic fibrosis transmembrane conductance regulator (CFTR), ENaC, and outer medullary potassium channel] suggests regulatory activating or inactivating interactions in defined morphogenic periods. This review focuses on embryonic patterns, at the mRNA and immunoprotein level, of the following transporter entities expressed in epithelial cell plasma membranes: ENaC; the chloride transporters CFTR, ClC-2, bumetanide-sensitive Na-K-Cl cotransporter, Cl/OH, and Cl/HCO(3); the sodium glucose transporter-glucose transporter; the sodium/hydrogen exchanger; the sodium-phosphate cotransporter; the ATPases; and AQP. The purpose of this article is to relate temporal and spatial expression patterns in embryonic and in early postnatal epithelia to developmental changes in organ structure and function.
Topics: Animals; Carrier Proteins; Epithelium; Humans; Kidney; Membranes
PubMed: 11097616
DOI: 10.1152/ajprenal.2000.279.6.F982 -
Biochimica Et Biophysica Acta Jan 2009Most biological membranes are extremely complex structures consisting of hundreds of different lipid and protein molecules. According to the famous fluid-mosaic model... (Review)
Review
Most biological membranes are extremely complex structures consisting of hundreds of different lipid and protein molecules. According to the famous fluid-mosaic model lipids and many proteins are free to diffuse very rapidly in the plane of the membrane. While such fast diffusion implies that different membrane lipids would be laterally randomly distributed, accumulating evidence indicates that in model and natural membranes the lipid components tend to adopt regular (superlattice-like) distributions. The superlattice model, put forward based on such evidence, is intriguing because it predicts that 1) there is a limited number of allowed compositions representing local minima in membrane free energy and 2) those energy minima could provide set-points for enzymes regulating membrane lipid compositions. Furthermore, the existence of a discrete number of allowed compositions could help to maintain organelle identity in the face of rapid inter-organelle membrane traffic.
Topics: Animals; Computer Simulation; Erythrocyte Membrane; Homeostasis; Humans; Lipid Metabolism; Lipids; Membrane Fluidity; Membrane Lipids; Membrane Microdomains; Membranes; Models, Biological; Models, Theoretical; Molecular Structure
PubMed: 19007747
DOI: 10.1016/j.bbamem.2008.10.004 -
Biochimica Et Biophysica Acta Jan 2009Without any exaggeration, cholesterol is one of the most important lipid species in eukaryotic cells. Its effects on cellular membranes and functions range from purely... (Review)
Review
Without any exaggeration, cholesterol is one of the most important lipid species in eukaryotic cells. Its effects on cellular membranes and functions range from purely mechanistic to complex metabolic ones, besides which it is also a precursor of the sex hormones (steroids) and several vitamins. In this review, we discuss the biophysical effects of cholesterol on the lipid bilayer, in particular the ordering and condensing effects, concentrating on the molecular level or inter-atomic interactions perspective, starting from two-component systems and proceeding to many-component ones e.g., modeling lipid rafts. Particular attention is paid to the roles of the methyl groups in the cholesterol ring system, and their possible biological function. Although our main research methodology is computer modeling, in this review we make extensive comparisons between experiments and different modeling approaches.
Topics: Animals; Cholesterol; Computer Simulation; Humans; Hydrophobic and Hydrophilic Interactions; Lipid Bilayers; Membrane Lipids; Membranes; Models, Biological; Molecular Structure; Surface Properties
PubMed: 18823938
DOI: 10.1016/j.bbamem.2008.08.022 -
Biophysical Journal Jun 2023Functionally meaningful reversible protein-membrane interactions mediate many biological events. Fluorescence correlation spectroscopy (FCS) is increasingly used to...
Functionally meaningful reversible protein-membrane interactions mediate many biological events. Fluorescence correlation spectroscopy (FCS) is increasingly used to quantitatively study the non-reversible binding of proteins to membranes using lipid vesicles in solution. However, the lack of a complete description of the phase and statistical equilibria in the case of reversible protein-membrane partitioning has hampered the application of FCS to quantify the partition coefficient (K). In this work, we further extend the theory that describes membrane-protein partitioning to account for spontaneous protein-membrane dissociation and reassociation to the same or a different lipid vesicle. We derive the probability distribution of proteins on lipid vesicles for reversible binding and demonstrate that FCS is a suitable technique for accurate K quantification of membrane-protein reversible association. We also establish the limits to K determination by FCS studying the Cramer-Rao bound on the variance of the retrieved parameters. We validate the mathematical formulation against reaction-diffusion simulations to study phase and statistical equilibria and compare the K obtained from a computational FCS titration experiment with the experimental ground truth. Finally, we demonstrate the application of our methodology studying the association of anti-HIV broadly neutralizing antibody (10E8-3R) to the membrane.
Topics: Membrane Proteins; Membranes; Spectrometry, Fluorescence; Diffusion; Lipids
PubMed: 36698316
DOI: 10.1016/j.bpj.2023.01.026 -
Archaea (Vancouver, B.C.) 2012Archaeal viruses represent one of the least known territory of the viral universe and even less is known about their lipids. Based on the current knowledge, however, it... (Review)
Review
Archaeal viruses represent one of the least known territory of the viral universe and even less is known about their lipids. Based on the current knowledge, however, it seems that, as in other viruses, archaeal viral lipids are mostly incorporated into membranes that reside either as outer envelopes or membranes inside an icosahedral capsid. Mechanisms for the membrane acquisition seem to be similar to those of viruses infecting other host organisms. There are indications that also some proteins of archaeal viruses are lipid modified. Further studies on the characterization of lipids in archaeal viruses as well as on their role in virion assembly and infectivity require not only highly purified viral material but also, for example, constant evaluation of the adaptability of emerging technologies for their analysis. Biological membranes contain proteins and membranes of archaeal viruses are not an exception. Archaeal viruses as relatively simple systems can be used as excellent tools for studying the lipid protein interactions in archaeal membranes.
Topics: Archaeal Viruses; Lipids; Lipoproteins; Membrane Lipids; Membranes; Viral Proteins
PubMed: 23049284
DOI: 10.1155/2012/384919 -
Fake It 'Till You Make It-The Pursuit of Suitable Membrane Mimetics for Membrane Protein Biophysics.International Journal of Molecular... Dec 2020Membrane proteins evolved to reside in the hydrophobic lipid bilayers of cellular membranes. Therefore, membrane proteins bridge the different aqueous compartments... (Review)
Review
Membrane proteins evolved to reside in the hydrophobic lipid bilayers of cellular membranes. Therefore, membrane proteins bridge the different aqueous compartments separated by the membrane, and furthermore, dynamically interact with their surrounding lipid environment. The latter not only stabilizes membrane proteins, but directly impacts their folding, structure and function. In order to be characterized with biophysical and structural biological methods, membrane proteins are typically extracted and subsequently purified from their native lipid environment. This approach requires that lipid membranes are replaced by suitable surrogates, which ideally closely mimic the native bilayer, in order to maintain the membrane proteins structural and functional integrity. In this review, we survey the currently available membrane mimetic environments ranging from detergent micelles to bicelles, nanodiscs, lipidic-cubic phase (LCP), liposomes, and polymersomes. We discuss their respective advantages and disadvantages as well as their suitability for downstream biophysical and structural characterization. Finally, we take a look at ongoing methodological developments, which aim for direct in-situ characterization of membrane proteins within native membranes instead of relying on membrane mimetics.
Topics: Animals; Biomimetics; Biophysical Phenomena; Crystallography, X-Ray; Humans; Lipid Bilayers; Liposomes; Membrane Lipids; Membrane Proteins; Membranes; Models, Molecular; Nanostructures; Structure-Activity Relationship
PubMed: 33374526
DOI: 10.3390/ijms22010050 -
The EMBO Journal Oct 2020Focal adhesion kinase (FAK) is a key component of the membrane proximal signaling layer in focal adhesion complexes, regulating important cellular processes, including...
Focal adhesion kinase (FAK) is a key component of the membrane proximal signaling layer in focal adhesion complexes, regulating important cellular processes, including cell migration, proliferation, and survival. In the cytosol, FAK adopts an autoinhibited state but is activated upon recruitment into focal adhesions, yet how this occurs or what induces structural changes is unknown. Here, we employ cryo-electron microscopy to reveal how FAK associates with lipid membranes and how membrane interactions unlock FAK autoinhibition to promote activation. Intriguingly, initial binding of FAK to the membrane causes steric clashes that release the kinase domain from autoinhibition, allowing it to undergo a large conformational change and interact itself with the membrane in an orientation that places the active site toward the membrane. In this conformation, the autophosphorylation site is exposed and multiple interfaces align to promote FAK oligomerization on the membrane. We show that interfaces responsible for initial dimerization and membrane attachment are essential for FAK autophosphorylation and resulting cellular activity including cancer cell invasion, while stable FAK oligomerization appears to be needed for optimal cancer cell proliferation in an anchorage-independent manner. Together, our data provide structural details of a key membrane bound state of FAK that is primed for efficient autophosphorylation and activation, hence revealing the critical event in integrin mediated FAK activation and signaling at focal adhesions.
Topics: Animals; Avian Proteins; Chickens; Enzyme Activation; Focal Adhesion Protein-Tyrosine Kinases; HEK293 Cells; Humans; Membranes; Protein Multimerization; Structure-Activity Relationship
PubMed: 32779739
DOI: 10.15252/embj.2020104743 -
Cell Calcium Jun 2017One of the largest challenges in cell biology is to map the lipid composition of the membranes of various organelles and define the exact location of processes that... (Review)
Review
One of the largest challenges in cell biology is to map the lipid composition of the membranes of various organelles and define the exact location of processes that control the synthesis and distribution of lipids between cellular compartments. The critical role of phosphoinositides, low-abundant lipids with rapid metabolism and exceptional regulatory importance in the control of almost all aspects of cellular functions created the need for tools to visualize their localizations and dynamics at the single cell level. However, there is also an increasing need for methods to determine the cellular distribution of other lipids regulatory or structural, such as diacylglycerol, phosphatidic acid, or other phospholipids and cholesterol. This review will summarize recent advances in this research field focusing on the means by which changes can be described in more quantitative terms.
Topics: Animals; Cell Compartmentation; Humans; Lipids; Membranes; Molecular Imaging; Protein Binding; Protein Domains
PubMed: 28088320
DOI: 10.1016/j.ceca.2016.12.008 -
Lipid Bilayers Manipulated through Monolayer Technologies for Studies of Channel-Membrane Interplay.Biological & Pharmaceutical Bulletin 2018Fluidity and mosaicity are two critical features of biomembranes, by which membrane proteins function through chemical and physical interactions within a bilayer. To... (Review)
Review
Fluidity and mosaicity are two critical features of biomembranes, by which membrane proteins function through chemical and physical interactions within a bilayer. To understand this complex and dynamic system, artificial lipid bilayer membranes have served as unprecedented tools for experimental examination, in which some aspects of biomembrane features have been extracted, and to which various methodologies have been applied. Among the lipid bilayers involving liposomes, planar lipid bilayers and nanodiscs, recent developments of lipid bilayer methods and the results of our channel studies are reviewed herein. Principles and techniques of bilayer formation are summarized, which have been extended to the current techniques, where a bilayer is formed from lipid-coated water-in-oil droplets (water-in-oil bilayer). In our newly developed method, termed the contact bubble bilayer (CBB) method, a water bubble is blown from a pipette into a bulk oil phase, and monolayer-lined bubbles are docked to form a bilayer through manipulation by pipette. An asymmetric bilayer can be readily formed, and changes in composition in one leaflet were possible. Taking advantage of the topological configuration of the CBB, such that the membrane's hydrophobic interior is contiguous with the surrounding bulk organic phase, oil-dissolved substances such as cholesterol were delivered directly to the bilayer interior to perfuse around the membrane-embedded channels (membrane perfusion), and current recordings in the single-channel allowed detection of immediate changes in the channels' response to cholesterol. Chemical and mechanical manipulation in each monolayer (monolayer technology) allows the examination of dynamic channel-membrane interplay.
Topics: Animals; Cell Membrane; Humans; Hydrophobic and Hydrophilic Interactions; Ion Channels; Lipid Bilayers; Membranes
PubMed: 29491206
DOI: 10.1248/bpb.b17-00708 -
PloS One 2017The fetal membrane surrounds the fetus during pregnancy and is a thin tissue composed of two layers, the chorion and the amnion. While rupture of this membrane normally...
The fetal membrane surrounds the fetus during pregnancy and is a thin tissue composed of two layers, the chorion and the amnion. While rupture of this membrane normally occurs at term, preterm rupture can result in increased risk of fetal mortality and morbidity, as well as danger of infection in the mother. Although structural changes have been observed in the membrane in such cases, the mechanical behaviour of the human fetal membrane in vivo remains poorly understood and is challenging to investigate experimentally. Therefore, the objective of this study was to develop simplified finite element models to investigate the mechanical behaviour and rupture of the fetal membrane, particularly its constituent layers, under various physiological conditions. It was found that modelling the chorion and amnion as a single layer predicts remarkably different behaviour compared with a more anatomically-accurate bilayer, significantly underestimating stress in the amnion and under-predicting the risk of membrane rupture. Additionally, reductions in chorion-amnion interface lubrication and chorion thickness (reported in cases of preterm rupture) both resulted in increased membrane stress. Interestingly, the inclusion of a weak zone in the fetal membrane that has been observed to develop overlying the cervix would likely cause it to fail at term, during labour. Finally, these findings support the theory that the amnion is the dominant structural component of the fetal membrane and is required to maintain its integrity. The results provide a novel insight into the mechanical effect of structural changes in the chorion and amnion, in cases of both normal and preterm rupture.
Topics: Algorithms; Amnion; Cervix Uteri; Chorion; Female; Fetal Membranes, Premature Rupture; Finite Element Analysis; Gestational Age; Humans; Labor, Obstetric; Pregnancy; Stress, Mechanical; Term Birth; Uterus
PubMed: 28350838
DOI: 10.1371/journal.pone.0171588