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Membranes: a meeting point for lipids, proteins and therapies.

Escribá PV, González-Ros JM, Goñi FM, Kinnunen PK, Vigh L, Sánchez-Magraner L, Fernández AM, Busquets X, Horváth I, Barceló-Coblijn G - J. Cell. Mol. Med. (2008)

Bottom Line: Moreover, their alteration has been associated with the development of numerous diseases.The present study reviews these interactions from the molecular and biomedical point of view, and the effects of their modulation on the physiological activity of cells, the aetiology of human diseases and the design of clinical drugs.In fact, the influence of lipids on protein function is reflected in the possibility to use these molecular species as targets for therapies against cancer, obesity, neurodegenerative disorders, cardiovascular pathologies and other diseases, using a new approach called membrane-lipid therapy.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Cell Biomedicine, Dept of Biology-IUNICS, University of the Balearic Islands, Palma de Mallorca, Spain. pablo.escriba@uib.es

ABSTRACT
Membranes constitute a meeting point for lipids and proteins. Not only do they define the entity of cells and cytosolic organelles but they also display a wide variety of important functions previously ascribed to the activity of proteins alone. Indeed, lipids have commonly been considered a mere support for the transient or permanent association of membrane proteins, while acting as a selective cell/organelle barrier. However, mounting evidence demonstrates that lipids themselves regulate the location and activity of many membrane proteins, as well as defining membrane microdomains that serve as spatio-temporal platforms for interacting signalling proteins. Membrane lipids are crucial in the fission and fusion of lipid bilayers and they also act as sensors to control environmental or physiological conditions. Lipids and lipid structures participate directly as messengers or regulators of signal transduction. Moreover, their alteration has been associated with the development of numerous diseases. Proteins can interact with membranes through lipid co-/post-translational modifications, and electrostatic and hydrophobic interactions, van der Waals forces and hydrogen bonding are all involved in the associations among membrane proteins and lipids. The present study reviews these interactions from the molecular and biomedical point of view, and the effects of their modulation on the physiological activity of cells, the aetiology of human diseases and the design of clinical drugs. In fact, the influence of lipids on protein function is reflected in the possibility to use these molecular species as targets for therapies against cancer, obesity, neurodegenerative disorders, cardiovascular pathologies and other diseases, using a new approach called membrane-lipid therapy.

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Schematic illustration of a biomembrane, depicting membrane lipid asymmetry as well as microdomains enriched in particular lipids and those induced by membrane proteins.
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fig03: Schematic illustration of a biomembrane, depicting membrane lipid asymmetry as well as microdomains enriched in particular lipids and those induced by membrane proteins.

Mentions: The fluid mosaic model proposed that membranes were formed by a fluid bilayer in which proteins and lipids could move freely [19], contributing greatly to our concept of a cell membrane. Initially, the mosaic model depicted by Singer and Nicolson referred to the random behaviour of the different proteins in the membrane bilayer as if in a ‘sea of lipids’. Today, the extended fluid mosaic model contemplates additional structural and functional restraints on membrane organization [5, 20]. In this context, most biological membranes are asymmetrical, both laterally and in cross-section. The cross-sectional asymmetry reflects the lipid composition of each leaflet (Fig. 3) [21]. The external leaflet of the plasma membrane (exoplasmic, E face) and the lumenal leaflets of internal organelles are highly enriched in choline-containing lipids such as PC and sphingomyelin (SM). In contrast, the cytoplasmic leaflet (protoplasmic, P face) is rich in amine-containing glycerophospho-lipids such as PE and phosphatidylserine (PS). Other minor phospholipids, such as phosphatidic acid (PA), phosphatidylinositol (PI), phosphatidylinositol-4-monophosphate (PIP) and phosphatidylinositol-4, 5-biphosphate (PIP2), are also enriched on the cytoplasmic face of the membrane where they participate in cell signalling [22, 23]. Interestingly, the membrane of the endoplasmic reticulum shows a symmetric lipid distribution and it primarily contains unsaturated glycerolipids that provide flexibility, and that facilitate the incorporation of newly synthesized proteins [24]. This is a clear example of how the same components may combine differently to yield different lipid organizations with features that adjust to their specific needs. Membrane heterogeneity is further achieved by lateral asymmetry in which membrane regions (basal, lateral, apical), and different specialized membrane regions or microdomains (lipid rafts, caveolae, coated pits, synaptosomes, etc.) [9, 25 and references therein] extend the mosaic nature of membranes. The formation of these domains in part results from the non-ideal mixing of lipids in membranes and in some cases, it is enhanced by the participation of certain cytoskeletal structures that underpin the lipid bilayer and that restrict the traffic of proteins and lipids.


Membranes: a meeting point for lipids, proteins and therapies.

Escribá PV, González-Ros JM, Goñi FM, Kinnunen PK, Vigh L, Sánchez-Magraner L, Fernández AM, Busquets X, Horváth I, Barceló-Coblijn G - J. Cell. Mol. Med. (2008)

Schematic illustration of a biomembrane, depicting membrane lipid asymmetry as well as microdomains enriched in particular lipids and those induced by membrane proteins.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4401130&req=5

fig03: Schematic illustration of a biomembrane, depicting membrane lipid asymmetry as well as microdomains enriched in particular lipids and those induced by membrane proteins.
Mentions: The fluid mosaic model proposed that membranes were formed by a fluid bilayer in which proteins and lipids could move freely [19], contributing greatly to our concept of a cell membrane. Initially, the mosaic model depicted by Singer and Nicolson referred to the random behaviour of the different proteins in the membrane bilayer as if in a ‘sea of lipids’. Today, the extended fluid mosaic model contemplates additional structural and functional restraints on membrane organization [5, 20]. In this context, most biological membranes are asymmetrical, both laterally and in cross-section. The cross-sectional asymmetry reflects the lipid composition of each leaflet (Fig. 3) [21]. The external leaflet of the plasma membrane (exoplasmic, E face) and the lumenal leaflets of internal organelles are highly enriched in choline-containing lipids such as PC and sphingomyelin (SM). In contrast, the cytoplasmic leaflet (protoplasmic, P face) is rich in amine-containing glycerophospho-lipids such as PE and phosphatidylserine (PS). Other minor phospholipids, such as phosphatidic acid (PA), phosphatidylinositol (PI), phosphatidylinositol-4-monophosphate (PIP) and phosphatidylinositol-4, 5-biphosphate (PIP2), are also enriched on the cytoplasmic face of the membrane where they participate in cell signalling [22, 23]. Interestingly, the membrane of the endoplasmic reticulum shows a symmetric lipid distribution and it primarily contains unsaturated glycerolipids that provide flexibility, and that facilitate the incorporation of newly synthesized proteins [24]. This is a clear example of how the same components may combine differently to yield different lipid organizations with features that adjust to their specific needs. Membrane heterogeneity is further achieved by lateral asymmetry in which membrane regions (basal, lateral, apical), and different specialized membrane regions or microdomains (lipid rafts, caveolae, coated pits, synaptosomes, etc.) [9, 25 and references therein] extend the mosaic nature of membranes. The formation of these domains in part results from the non-ideal mixing of lipids in membranes and in some cases, it is enhanced by the participation of certain cytoskeletal structures that underpin the lipid bilayer and that restrict the traffic of proteins and lipids.

Bottom Line: Moreover, their alteration has been associated with the development of numerous diseases.The present study reviews these interactions from the molecular and biomedical point of view, and the effects of their modulation on the physiological activity of cells, the aetiology of human diseases and the design of clinical drugs.In fact, the influence of lipids on protein function is reflected in the possibility to use these molecular species as targets for therapies against cancer, obesity, neurodegenerative disorders, cardiovascular pathologies and other diseases, using a new approach called membrane-lipid therapy.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Cell Biomedicine, Dept of Biology-IUNICS, University of the Balearic Islands, Palma de Mallorca, Spain. pablo.escriba@uib.es

ABSTRACT
Membranes constitute a meeting point for lipids and proteins. Not only do they define the entity of cells and cytosolic organelles but they also display a wide variety of important functions previously ascribed to the activity of proteins alone. Indeed, lipids have commonly been considered a mere support for the transient or permanent association of membrane proteins, while acting as a selective cell/organelle barrier. However, mounting evidence demonstrates that lipids themselves regulate the location and activity of many membrane proteins, as well as defining membrane microdomains that serve as spatio-temporal platforms for interacting signalling proteins. Membrane lipids are crucial in the fission and fusion of lipid bilayers and they also act as sensors to control environmental or physiological conditions. Lipids and lipid structures participate directly as messengers or regulators of signal transduction. Moreover, their alteration has been associated with the development of numerous diseases. Proteins can interact with membranes through lipid co-/post-translational modifications, and electrostatic and hydrophobic interactions, van der Waals forces and hydrogen bonding are all involved in the associations among membrane proteins and lipids. The present study reviews these interactions from the molecular and biomedical point of view, and the effects of their modulation on the physiological activity of cells, the aetiology of human diseases and the design of clinical drugs. In fact, the influence of lipids on protein function is reflected in the possibility to use these molecular species as targets for therapies against cancer, obesity, neurodegenerative disorders, cardiovascular pathologies and other diseases, using a new approach called membrane-lipid therapy.

Show MeSH
Related in: MedlinePlus