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Coats define the composition of carriers budding from organelles. In addition, coats interact with membrane tethers required for vesicular fusion. The yeast AP-3 (Adaptor Protein Complex 3) coat and the class C Vps/HOPS (HOmotypic fusion and Protein Sorting) tether follow this model as their interaction occurs at the carrier fusion step. Here we show that(More)
Nitric oxide (NO) is a radical and a gas, properties that allow NO to diffuse through membranes and potentially enable it to function as a "volume messenger." This study had two goals: first, to investigate the mechanisms by which NO functions as a modulator of neuronal excitability, and second, to compare NO effects produced by NO release from chemical NO(More)
Nitric oxide (NO), a gaseous messenger, has been reported to be involved in a variety of functions in the nervous system, ranging from neuronal pathfinding to learning and memory. We have shown previously that the application of NO via NO donors to growth cones of identified Helisoma buccal neurons B5 in vitro induces an increase in filopodial length, a(More)
Dysbindin assembles into the biogenesis of lysosome-related organelles complex 1 (BLOC-1), which interacts with the adaptor protein complex 3 (AP-3), mediating a common endosome-trafficking route. Deficiencies in AP-3 and BLOC-1 affect synaptic vesicle composition. However, whether AP-3-BLOC-1-dependent sorting events that control synapse membrane protein(More)
Post-mortem analysis has revealed reduced levels of the protein dysbindin in the brains of those suffering from the neurodevelopmental disorder schizophrenia. Consequently, mechanisms controlling the cellular levels of dysbindin and its interacting partners may participate in neurodevelopmental processes impaired in that disorder. To address this question,(More)
Mutations in Vps33 isoforms cause pigment dilution in mice (Vps33a, buff) and Drosophila (car) and the neurogenic arthrogryposis, renal dysfunction and cholestasis syndrome in humans (ARC1, VPS33B). The later disease is also caused by mutations in VIPAS39, (Vps33b interacting protein, apical-basolateral polarity regulator, SPE-39 homolog; ARC2), a protein(More)
Phosphatidylinositol-3-kinase (PI-3K) has been reported to affect neurite outgrowth both in vivo and in vitro. Here we investigated the signaling pathways by which PI-3K affects neurite outgrowth and growth cone motility in identified snail neurons in vitro. Inhibition of PI-3K with wortmannin (2 microM) or LY 294002 (25 microM) resulted in a significant(More)
The neuronal growth cone provides the sensory and motor structure that guides neuronal processes to their target. The ability of a growth cone to navigate correctly depends on its filopodia, which sample the environment by continually extending and retracting as the growth cone advances. Several second messengers systems that are activated upon contact with(More)
The electrical activity in developing and mature neurons determines the intracellular calcium concentration ([Ca(2+)]i), which in turn is translated into biochemical activities through various signaling cascades. Electrical activity is under control of neuromodulators, which can alter neuronal responses to incoming signals and increase the fidelity of(More)
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