Cell Biology of the BLOC-1 Complex Subunit Dysbindin, a Schizophrenia Susceptibility Gene

Mullin, Ariana P.; Gokhale, Avanti; Larimore, Jennifer L.; Faúndez, Víctor

doi:10.1007/s12035-011-8183-3

Cited by 61 publications

(74 citation statements)

References 123 publications

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“…Dysb associates with SVs and appears to promote homeostasis downstream or independently of Ca 2+ influx at the synapse. In mammals and flies, Dysb associates with seven other proteins to form BLOC-1 (biogenesis of lysosome-related organelles), a complex implicated in several aspects of membrane trafficking and fusion (Mullin et al 2011. Genetic interaction experiments support the idea that the BLOC-1 components Snapin and Blos-1 cooperate with Dysb to mediate homeostatic plasticity in Drosophila (Dickman et al 2012;Mullin et al 2015), and like Dysb, Snapin localizes to SVs (Dickman et al 2012).…”

Section: Homeostatic Plasticitymentioning

confidence: 86%

Transmission, Development, and Plasticity of Synapses

Harris¹,

2015

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Chemical synapses are sites of contact and information transfer between a neuron and its partner cell. Each synapse is a specialized junction, where the presynaptic cell assembles machinery for the release of neurotransmitter, and the postsynaptic cell assembles components to receive and integrate this signal. Synapses also exhibit plasticity, during which synaptic function and/or structure are modified in response to activity. With a robust panel of genetic, imaging, and electrophysiology approaches, and strong evolutionary conservation of molecular components, Drosophila has emerged as an essential model system for investigating the mechanisms underlying synaptic assembly, function, and plasticity. We will discuss techniques for studying synapses in Drosophila, with a focus on the larval neuromuscular junction (NMJ), a well-established model glutamatergic synapse. Vesicle fusion, which underlies synaptic release of neurotransmitters, has been well characterized at this synapse. In addition, studies of synaptic assembly and organization of active zones and postsynaptic densities have revealed pathways that coordinate those events across the synaptic cleft. We will also review modes of synaptic growth and plasticity at the fly NMJ, and discuss how pre-and postsynaptic cells communicate to regulate plasticity in response to activity. KEYWORDS FlyBook; Drosophila; synapse; neurotransmitter release; synaptic plasticity; active zone; synaptic vesicle TABLE OF CONTENTS Abstract 345Introduction 345

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Section: Homeostatic Plasticitymentioning

confidence: 86%

Transmission, Development, and Plasticity of Synapses

Harris¹,

2015

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“…The dysbindincontaining BLOC-1 complex is a component of the endosomal protein sorting and compartmental machinery (43,44). Abnormalities in Ebony protein sorting may lead to abnormalities in ubiquitylation, protein instability, or malfunction of the enzyme.…”

Section: Glutamatergic Functions and Memorymentioning

confidence: 99%

Schizophrenia susceptibility gene dysbindin regulates glutamatergic and dopaminergic functions via distinctive mechanisms in Drosophila

Shao

Shuai

Wang

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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The dysfunction of multiple neurotransmitter systems is a striking pathophysiological feature of many mental disorders, schizophrenia in particular, but delineating the underlying mechanisms has been challenging. Here we show that manipulation of a single schizophrenia susceptibility gene, dysbindin, is capable of regulating both glutamatergic and dopaminergic functions through two independent mechanisms, consequently leading to two categories of clinically relevant behavioral phenotypes. Dysbindin has been reported to affect glutamatergic and dopaminergic functions as well as a range of clinically relevant behaviors in vertebrates and invertebrates but has been thought to have a mainly neuronal origin. We find that reduced expression of Drosophila dysbindin (Ddysb) in presynaptic neurons significantly suppresses glutamatergic synaptic transmission and that this glutamatergic defect is responsible for impaired memory. However, only the reduced expression of Ddysb in glial cells is the cause of hyperdopaminergic activities that lead to abnormal locomotion and altered mating orientation. This effect is attributable to the altered expression of a dopamine metabolic enzyme, Ebony, in glial cells. Thus, Ddysb regulates glutamatergic transmission through its neuronal function and regulates dopamine metabolism by regulating Ebony expression in glial cells.dystrobrevin binding protein 1 | glutamate | glia

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“…Variations in the same human gene coding for dysbindin, DTNBP1, are strongly associated with schizophrenia in some populations, suggesting that the function of dysbindin is impaired in DTNBP1-associated schizophrenia (17). Biochemical fractionation of dysbindin and its developmental regulation in brain suggest that dysbindin functions in neurons in its context as a subunit of BLOC-1 (18). Thus, BLOC-1 is not only a pivotal player in LRO biogenesis and HPS7-9 but may also have significance for the molecular basis for schizophrenia.…”

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confidence: 99%