Determinants of calcineurin binding to model membranes.
The biochemical factors that lead to membrane targeting of the Ser/Thr protein phosphatase calcineurin were examined using model phospholipid membranes. The interaction of myristoyl- and non-myristoylcalcineurin with lipid surfaces was investigated as a function of negatively charged phospholipids, diacylglycerol, Ca2+, and calmodulin. The data indicate that calcineurin binding to phospholipid monolayers both is myristoyl-independent and is mediated by anionic phospholipids and/or diacylglycerol. Although the effect of Ca2+ on calcineurin-lipid binding is minor, calmodulin altered the binding of calcineurin to the lipid membrane in a Ca2+-dependent manner. Experiments with a constitutively active form of calcineurin that does not bind calmodulin indicated that the effect required the interaction of calcineurin with calmodulin. Our results suggest that phosphatidylserine, diaclyglycerol, and calmodulin may mediate the lipid binding properties of calcineurin in vivo.
Kennedy
M T
MT
Department of Biochemistry and Molecular Biology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Brockman
H
H
Rusnak
F
F
D000818:Animals; D019703:Calcineurin / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D019281:Dimerization; D008051:Lipid Bilayers / Q000378:metabolism*; D009227:Myristic Acids / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding; D051381:Rats
D002147:Calmodulin; D004075:Diglycerides; D008051:Lipid Bilayers; D009227:Myristic Acids; D010718:Phosphatidylserines; D010743:Phospholipids; C050294:1-palmitoyl-2-oleoylglycero-3-phosphoserine; D019703:Calcineurin; D002118:Calcium