Although the deep conservation of charge density and hydrophobic moment suggests that they play a role in complexin function, the inhibition of spontaneous fusion does not require either feature in worm (this study) and hydrophobicity is superfluous in fly as well (Cho et al., 2014).
Nevertheless, our data indicate that the nucleation and propagation function of the AH domain is universal for proper complexin function across species.
Complexin activates and clamps neurotransmitter release; impairing complexin function decreases synchronous, but increases spontaneous and asynchronous synaptic vesicle exocytosis.
These findings indicate that hydrophobic residues in the AH domain do not play a critical conserved role in complexin function.
Genetic interaction studies in hippocampal neurons showed that complexins regulate release similarly in the absence or presence of synaptotagmin-1, indicating that complexins function independently of synaptotagmin-1 (Xue et al., 2007, 2010), but this finding does not exclude the notion that complexins and synaptotagmin-1 may cooperate in regulating release.
Alternatively, the high negative charge and hydrophobic moment of the AH domain may be relevant for other complexin functions.
For 250 μM Ca2+, in the absence of complexin the fitted function is f(t) = 0.0026 + 0.027e−t/2.98 and it is three times more likely compared to a two-exponential fit, and in the presence of 5 μM complexin the fitted function is f(t) = 0.0005 + 0.10e−t/0.89 + 0.011e−t/14.5 and it is 10 times more likely compared to a single exponential fit.
For 500 μM Ca2+, in the absence of complexin the fitted function is f(t) = 0.0014 + 2.66e−t/0.11 + 0.22e−t/1.94 and it is 10 times more likely compared to a single exponential fit, and in the presence of 5 μM complexin the fitted function is f(t) = 0.0006 + 0.42e−t/0.81 + 0.05e−t/4.76 and it is 10 times more likely compared to a single exponential fit.
For 500 μM Ca2+, in the absence of complexin the fitted function is f(t) = 0.0015 + 0.096e−t/1.93 and it is 10 times more likely compared to a two-exponential fit, and in the presence of 5 μM complexin the fitted function is f(t) = 0.0021 + 0.084e−t/2.38 + 0.18e−t/0.36 and it is 10 times more likely compared to a single exponential fit.
Trans SNAP receptor (SNARE, where SNAP is defined as soluble NSF attachment protein, and NSF is defined as N-ethylmaleimide sensitive factor) complexes catalyze syN-ethylmaleimide sensitivebind complexin, but the factoron of complexes binding to SNARE catalyzesynaptics unclear.
