Am. Vaccaro et al., SAPOSIN-C INDUCES PH-DEPENDENT DESTABILIZATION AND FUSION OF PHOSPHATIDYLSERINE-CONTAINING VESICLES, FEBS letters, 349(2), 1994, pp. 181-186
We have previously shown that saposin C (Sap C), a glucosylceramidase
activator protein, interacts with phosphatidylserine (PS) large unilam
ellar vesicles (LUV), promoting the glucosylceramidase binding to the
bilayer [(1993) FEBS Lett. 336, 159-162]. In the present paper the con
sequences of the Sap C interaction on the lipid organization of the ve
sicles are reported. It was found that Sap C perturbs the PS bilayer a
s shown by the release of an encapsulated fluorescent dye. Three diffe
rent procedures, resonance energy transfer, gel filtration and electro
n microscopy, indicated that the activator protein is also able to mak
e PS liposomes fuse. The effects of Sap C on PS vesicles were observed
at low but not at neutral pH. The lipid composition of the bilayer al
so affected the Sap C-induced destabilization; in fact, the presence o
f PS in mixed LUV was essential for significant leakage to occur. Thes
e results demonstrate for the first time that Sap C is a protein capab
le of destabilizing and fusing acidic phospholipid-containing membrane
s in a pH-dependent fashion.