Single-Stage Repair of Complex Congenital Aortic Arch Pathology With Dissection and Aneurysm in an Adult.

Efficient membrane trafficking is critical for a variety of biological processes, performing key functions in all cell types. In neurons, membrane trafficking is particularly important given the long distances between cell bodies and synapses and the need to coordinate rapid vesicle recycling during neurotransmission. Hence, many specialized pathways have evolved in neurons to maintain robust, rapid, and reliable membrane trafficking to meet the unique challenges associated with neuronal development, growth, function, and plasticity (; ; ). Ultimately, these pathways are necessary to maintain stable information transfer in the nervous system. The biogenesis of lysosome-related organelles complex 1 (BLOC-1) is an intriguing candidate to ensure stable neuronal membrane trafficking. In the nervous system, BLOC-1 serves important roles in the trafficking of synaptic vesicles, postsynaptic receptors, and endosomal structures (; ; ; ; ; ; ; ). Biochemically, the BLOC-1 forms a stable octameric complex composed of Dysbindin, Snapin, Muted, Pallidin, and Blos1-4 (; ; ; ; ; ), Recent studies indicate the existence of two BLOC-1 subcomplexes, one consisting of Dysbindin, Snapin, Muted, and Blos2, and the other consisting of Pallidin, Blos1, Blos3, and Blos4 (; ). However, genetic and cell biological studies have led to conflicting models regarding whether BLOC-1 components necessarily function as a unit or independently, with some phenotypes, such as pigmentation and vesicle trafficking, shared by mutants in BLOC-1 (; ; ; ; ), while distinctions are observed in other functions (; ; ; ; ; ). To date, no study has systematically mutated all eight BLOC-1 components to directly test for shared versus distinct functions of the entire BLOC-1. is a powerful model system to uncover fundamental functions of the BLOC-1. First, highly conserved homologues of all eight BLOC-1 genes are encoded in (; ). Second, there is strong evidence that the same biochemical interactions between BLOC-1 subunits observed in mammals are conserved in flies (). Third, there are a wealth of genetic resources to interrogate the functions of all eight BLOC-1 components, particularly with the recent introduction of specific CRISPR gene editing approaches. One component of the BLOC-1, the schizophrenia susceptibility gene , was discovered in a forward genetic screen to be necessary for a well-studied form of synaptic plasticity modeled at the glutamatergic fly neuromuscular junction (NMJ) called presynaptic homeostatic potentiation (PHP) (). Although subsequent work found another BLOC-1 component, , to be necessary for PHP, two other components, and , were found to be dispensable for this process (; ). Intriguingly, Dysbindin and Snapin localize to synaptic vesicle pools (; ), while Pallidin localizes to the neuronal cytoskeleton (), suggesting a model in which localization might predict function of BLOC-1 components.