LAUSR

MUNC18-1/Syntaxin binding protein-1 (Stxbp1), binds Syntaxin-1. Together, these proteins regulate synaptic vesicle exocytosis and have a separate role in neuronal viability. In MUNC18-1/Stxbp1 null mutant neurons, Syntaxin-1 protein levels are 70% reduced. Here, we show that Dynamin-1 protein levels are reduced at least to the same extent, and DNM1 transcript levels are 50% reduced in MUNC18-1/Stxbp1 null mutant brain. Several, but not all, other endocytic proteins were also reduced, but to a lesser extent. The reduced Dynamin-1 expression was not observed in SNAP25 and MUNC13-1/2 null mutants, in which synaptic vesicle exocytosis is also blocked. Co-immunoprecipitation experiments demonstrated that Dynamin-1 and MUNC18-1 do not bind directly. Furthermore, MUNC18-1 levels were unaltered in neurons lacking all three Dynamin paralogs. Finally, overexpression of Dynamin-1 was not sufficient to rescue neuronal viability in MUNC18-1/Stxbp1 null mutant neurons, thus the reduction in Dynamin-1 is not the single cause for neurodegeneration of these neurons. The reduction of Dynamin-1 protein and mRNA, and other endocytosis proteins in Stxbp1 null mutant neurons suggests that MUNC18-1 directly or indirectly controls protein and mRNA levels of other presynaptic genes.