INTERACTIONS OF SYNAPSIN-I WITH PHOSPHOLIPIDS - POSSIBLE ROLE IN SYNAPTIC VESICLE CLUSTERING AND IN THE MAINTENANCE OF BILAYER STRUCTURES

Synapsin I is a synaptic vesicle-specific phosphoprotein composed of a globular and hydrophobic head and of a proline-rich, elongated and ba sic tail. Synapsin I binds with high affinity to phospholipid and prot ein components of synaptic vesicles. The head region of the protein ha s a very high surface activity, strongly interacts with acidic phospho lipids and penetrates the hydrophobic core of the vesicle membrane. In the present paper, we have investigated the possible functional effec ts of the interaction between synapsin I and vesicle phospholipids. Sy napsin I enhances both the rate and the extent of Ca2+-dependent membr ane fusion, although it has no detectable fusogenic activity per se. T his effect, which appears to be independent of synapsin I phosphorylat ion and localized to the head region of the protein, is attributable t o aggregation of adjacent vesicles. The facilitation of Ca2+-induced l iposome fusion is maximal at 50-80% of vesicle saturation and then dec reases steeply, whereas vesicle aggregation does not show this biphasi c behavior. Association of synapsin I with phospholipid bilayers does not induce membrane destabilization. Rather, P-31-nuclear magnetic res onance spectroscopy demonstrated that synapsin I inhibits the transiti on of membrane phospholipids from the bilayer (L(alpha)) to the invert ed hexagonal (H(II)) phase induced either by increases in temperature or by Ca2+. These properties might contribute to the remarkable select ivity of the fusion of synaptic vesicles with the presynaptic plasma m embrane during exocytosis.