Chemistry Reference
In-Depth Information
Chapter 3
Electrostatic Interactions in Membrane Fusion
The role of electrostatic interactions in SNARE-mediated lipid
bilayer fusion and the putative function of synaptotagmin-1, the
Ca
2
+
trigger of fusion, are investigated.
3.1 Introduction
Presynaptic nerve terminals convert electrical signals into chemical signals that tar-
get other neurons or somatic cells. The chemical signalling molecules are con-
tained in synaptic vesicles and the conversion is mediated by a depolarisation of
the plasma membrane, which causes an influx of
Ca
2
+
through voltage activated
Ca
2
+
-channels. The increase of the local cytoplasmic
Ca
2
+
concentration triggers
the submillisecond fusion of synaptic vesicles with the plasma membrane result-
ing in neuronal exocytosis i.e. release of neurotransmitters. Membrane fusion is
mediated by the assembly of SNARE proteins (Fig.
3.1
) including the R-SNARE
synaptobrevin-2 on the synaptic vesicle and the Q-SNAREs syntaxin-1A and SNAP-
25 on the plasma membrane [
1
,
2
]. SNARE assembly involves the conserved,
membrane-adjacent SNARE motifs, proceeds from the N-terminus towards the
C-terminal membrane anchors, and results in the formation of a tight coil-coil struc-
ture which pulls the membranes together and overcomes the energy barrier of mem-
brane fusion. Though there is no direct evidence, membrane fusion itself is widely
speculated to proceed via a sequence of steps involving increased membrane curva-
tion, hemi-fusion i.e. fusion of only the outer lipid leaflet, pore formation and finally
complete fusion as shown in the lower panel of Fig.
3.1
.
