Human proteolipid protein (PLP) mediates winding and adhesion of phospholipid membranes but prevents their fusion

Proteolipid protein (PLP or lipophilin) is a highly conserved, strongly hyd rophobic, integral membrane protein, and is the major protein component of central nervous system myelin. Although PLP has been implicated in many fun ctions, its in vivo role is still uncertain. Here, we report the investigat ion of PLP's putative adhesive function using purified PLP and reconstitute d phospholipid vesicles made of either 100% phosphatidylcholine (PC), or a mixture of 92% PC and 8% phosphatidylserine (PS), by weight. PLP-induced ch anges in the phospholipid bilayer surfaces were directly examined by transm ission electron microscopy. We found that upon the introduction of PLP, lar ger lipid vesicles became smaller and unilamellar. At the PLP:lipid molar r atio of 1.20, vesicle membranes rolled onto themselves forming 'croissant'- like structures that subsequently adhered to each other. The phenomena of P LP-induced bilayer rolling and adhesion were dependent on the concentration of PLP and the period of incubation, but were independent of the presence of calcium and types of phospholipids (PC or PC:PS), Furthermore, the prese nce of PLP in the lipid bilayers prevented the fusion of membranes. These f indings show that PLP can induce membrane 'winding' while preventing the fu sion of adjacent lipid bilayers. Hence, our data provide direct evidence fo r PLP's suspected function of membrane adhesion, and also suggest that PLP could potentially play a role in the formation of the myelin sheath. (C) 19 98 Elsevier Science B.V. All rights reserved.