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 basic tail. Synapsin I binds with high affinity to phospholipid and protein components of synaptic vesicles. The head region of the protein has a very high surface activity, strongly interacts with acidic phospholipids and penetrates the hydrophobic core of the vesicle membrane. In the present paper, we have investigated the possible functional effects of the interaction between synapsin I and vesicle phospholipids. Synapsin I enhances both the rate and the extent of Ca(2+)-dependent membrane fusion, although it has no detectable fusogenic activity per se. This effect, which appears to be independent of synapsin I phosphorylation and localized to the head region of the protein, is attributable to aggregation of adjacent vesicles. The facilitation of Ca(2+)-induced liposome fusion is maximal at 50-80% of vesicle saturation and then decreases steeply, whereas vesicle aggregation does not show this biphasic behavior. Association of synapsin I with phospholipid bilayers does not induce membrane destabilization. Rather, 31P-nuclear magnetic resonance spectroscopy demonstrated that synapsin I inhibits the transition of membrane phospholipids from the bilayer (L alpha) to the inverted hexagonal (HII) phase induced either by increases in temperature or by Ca2+. These properties might contribute to the remarkable selectivity of the fusion of synaptic vesicles with the presynaptic plasma membrane during exocytosis.
Benfenati
F
F
Institute of Human Physiology, University of Modena, Italy.
Valtorta
F
F
Rossi
M C
MC
Onofri
F
F
Sihra
T
T
Greengard
P
P
D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium; D002417:Cattle; D002784:Cholesterol; D008051:Lipid Bilayers; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008563:Membrane Lipids / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D010758:Phosphorus; D010766:Phosphorylation; D051381:Rats; D013050:Spectrometry, Fluorescence; D016704:Synapsins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000648:ultrastructure
D008051:Lipid Bilayers; D008563:Membrane Lipids; D010743:Phospholipids; D016704:Synapsins; D010758:Phosphorus; D002784:Cholesterol; D002118:Calcium