[Physical arrangement of membrane lipids susceptible to being used in the process of cell sorting of proteins].
Detection of immiscible lipid domains in biological membranes offers an alternative support to protein sorting. Liquid ordered domains ("rafts") comprising cholesterol and saturated sphingolipids incorporate saturated glycosyl-phosphatidylinositol (GPI)-anchored or acylated (palmitoyl- and myristoyl-) proteins or particular transmembrane protein sequences. These lipid domains can be isolated in the form of Detergent resistant membranes (DRM) from biological plasma membrane preparations. Caveolae appear to be a differentiated fraction of plasma membranes comprising such numerous cross-linked microdomains associated with caveolin in different cell types. While the biological relevance of such membrane domains is evidenced in vivo by co-patching of proteins sharing the identical affinity for sphingolipids and by the disruption of co-patching following cell cholesterol depletion, only a few physical studies confort the principle of membrane heterogeneity. Results are now presented where cholesterol addition in a tertiary lipid mixture forces outphase-separation, as a realistic model where the lipid segregation can promote protein sorting to the segregated Lo phase. A lipid mixture comprising phosphatidylserine, phosphatidylethanolamine and sphingomyelin of natural origin in the ratio (1/4/3: mole/mole) has been rendered neatly heterogeneous after the addition of cholesterol (27 mole%). Xray diffraction (Small angle Xray scattering) showed the splitting of two neatly resolved lamellar diffractions in the presence of cholesterol. Above 37 degrees C the heterogeneity was traceable by a broadened diffraction spot up to the complete get-to-liquid transition of sphingomyelin at temperatures > 40 degrees C where the spot became again symmetrical and narrow. The large temperature range where the immiscible lamellar phases are detected, the specific requirement for cholesterol association with sphingomyelin, the positive influence of calcium and the reversibility of domain formation support the occurrence for such domains at the inner side of the plasma membrane whereon lipids-bound proteins concentrate.
Wolf
C
C
CHU Saint-Antoine-CNRS, Paris, France.
Quinn
P
P
Koumanov
K
K
Chachaty
C
C
Tenchov
B
B
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002784:Cholesterol / Q000302:isolation & purification / Q000378:metabolism; D004847:Epithelial Cells / Q000502:physiology; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D008563:Membrane Lipids / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D010743:Phospholipids / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D013107:Sphingolipids / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism
D017261:Glycosylphosphatidylinositols; D008563:Membrane Lipids; D008565:Membrane Proteins; D010743:Phospholipids; D011506:Proteins; D013107:Sphingolipids; D013109:Sphingomyelins; D002784:Cholesterol
Arrangement physique des lipides membranaires susceptibles d'être utilisés par les processus d'adressage cellulaire des protéines.