The cytoplasmic domain of myelin glycoprotein P0 interacts with negatively charged phospholipid bilayers.
The intracellular COOH-terminal domain of the glycoprotein, P0, has been proposed to be involved in the formation of the major dense line of peripheral myelin. We have addressed this hypothesis by generating and subsequently isolating a peptide fragment that contains 65 of the 69 residues of the cytoplasmic region of rat P0. This peptide, termed P0(intra), bound to artificial phospholipid vesicles and caused their rapid aggregation. The peptide-induced aggregation of membrane bilayers appeared to result from ionic interactions, since P0(intra) vesicle association was decreased by 1) reducing the phosphatidylserine content of the membranes, 2) increasing the NaCl concentration of the surrounding buffer, or 3) elevating the divalent cation concentration within the buffers. Cationic disc gel electrophoresis of P0(intra) revealed at least four charge isoforms of the peptide. Treatment of sciatic nerve slices with phorbol ester prior to isolation of P0(intra) increased the amount of the more negatively charged species, suggesting that at least some of the charge heterogeneity of the peptide can be attributed to differing phosphorylation states. The ability of P0(intra) to bind to phospholipid bilayers implies that the cytoplasmic domain of P0 may be responsible for the formation and maintenance of the myelin major dense line.
Ding
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Discovery Research Group, Gliatech Inc., Cleveland, Ohio 44122.
Brunden
K R
KR
D000818:Animals; D002852:Chromatography, Ion Exchange; D003593:Cytoplasm / Q000378:metabolism; D004563:Electrochemistry; D004591:Electrophoresis, Polyacrylamide Gel; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism; D018993:Myelin P0 Protein; D009185:Myelin Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D008051:Lipid Bilayers; D008563:Membrane Lipids; D018993:Myelin P0 Protein; D009185:Myelin Proteins; D010446:Peptide Fragments; D010743:Phospholipids