Anti-SYT1 monoclonal antibody, clone 3H2 2D7

Objectives. Cocaine is the second most used illegal drug in Europe. The transition from use to dependence involves both genetic and environmental factors. Genetic variation in neurotransmitter systems is involved in the susceptibility to cocaine dependence. We examined the possible contribution to cocaine dependence of 16 genes involved in the cellular machinery that controls neurotransmitter release: genes encoding proteins of the SNARE complex (STX1A, SNAP25, VAMP1 and VAMP2), fusion control elements (SYT1, SYT2, CPLX1, CPLX2, CPLX3 and CPLX4) and regulatory elements (STXBP1, SYP, SNPH, NSF, NAPA and RAB3A). Methods. We genotyped 121 SNPs, selected according to genetic coverage criteria, in 360 cocaine-dependent patients and 360 controls from Spain. Results. Single and multiple-marker analyses revealed a strong association between cocaine dependence and the NSF gene, encoding the N-ethylmaleimide-sensitive factor (P = 5.1e-04, OR = 2.44 (1.45-4.00) and P = 0.001, OR = 1.82 (1.28-2.59), respectively). The presence and absence of psychotic symptoms were also studied. Interestingly, when we considered the time between initial consumption and the onset of cocaine dependence, we observed that the association was mainly restricted to the group of patients that rapidly developed drug dependence (<= 2 years; P = 2.98e-06, OR = 1.33 (1.20-1.47)). Conclusions. Our data show preliminary evidence that NSF may predispose not only to cocaine dependence, but also to an early onset of the dependence.

Fibroblast growth factor (FGF) 1 is known to be released in response to stress conditions as a component of a multiprotein aggregate containing the p40 extravescicular domain of p65 synaptotagmin (Syt) 1 and S100A13, Since FGF1 is a Cu2+-binding protein and Cu2+ is known to induce its dimerization, we evaluated the capacity of recombinant FGF1, p40 Syt1, and S100A13 to interact in a cell-free system and the role of Cu2+ in this interaction. We report that FGF1, p40 Syt1, and S100A13 are able to bind Cu2+ With Similar affinity and to interact in the presence of Cu2+ to form a multiprotein aggregate which is resistant to low concentrations of SDS and sensitive to reducing conditions and ultracentrifugation, The formation of this aggregate in the presence of Cu2+ is dependent on the presence of S100A13 and is mediated by cysteine-independent interactions between S100A13 and either FGF1 or p40 Syt1, Interestingly, S100A13 is also able to interact in the presence of Cu2+ with Cys-free FGF1 and this observation may account for the ability of S100A13 to export Cys-free FGF1 in response to stress. Lastly, tetrathiomolybdate, a Cu2+ chelator, significantly represses in a dose-dependent manner the heat shock-induced release of FGF1 and S100A13, These data suggest that S100A13 may be involved in the assembly of the multiprotein aggregate required for the release of FGF1 and that Cu2+ oxidation may be an essential post-translational intracellular modifier of this process.