Polyunsaturation in cell membranes and lipid bilayers and its effects on membrane proteins.
The effect of variation of the degree of cis-unsaturation on cell membrane protein functioning was investigated using a model lipid bilayer system and protein kinase C (PKC). This protein is a key element of signal transduction. Furthermore it is representative of a class of extrinsic membrane proteins that show lipid dependent interactions with cell membranes. To test for dependence of activity on the phospholipid unsaturation, experiments were devised using a vesicle assay system consisting of phosphatidylcholine (PC) and phosphatidylserine (PS) in which the unsaturation was systematically varied. Highly purified PKC alpha and epsilon were obtained using the baculovirus-insect cell expression system. It was shown that increased PC unsaturation elevated the activity of PKC alpha. By contrast, increasing the unsaturation of PS decreased the activity of PKC alpha, and to a lesser extent PKC epsilon. This result immediately rules out any single lipid bilayer physical parameter, such as lipid order, underlying the effect. It is proposed that while PC unsaturation effects are explainable on the basis of a contribution to membrane surface curvature stress, the effects of PS unsaturation may be due to specific protein-lipid interactions. Overall, the results indicate that altered phospholipid unsaturation in cell membranes that occurs in certain disease states such as chronic alcoholism, or by dietary manipulations, are likely to have profound effects on signal transduction pathways involving PKC and similar proteins.
Slater
S J
SJ
Department of Pathology and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Kelly
M B
MB
Yeager
M D
MD
Larkin
J
J
Ho
C
C
Stubbs
C D
CD
D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D004789:Enzyme Activation; D005224:Fats, Unsaturated / Q000378:metabolism*; D008051:Lipid Bilayers; D008565:Membrane Proteins / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats
D005224:Fats, Unsaturated; D008051:Lipid Bilayers; D008565:Membrane Proteins; D010718:Phosphatidylserines; D011493:Protein Kinase C