β-dystrobrevin, a member of the dystrophin-related protein family

Blake, Derek J.; Nawrotzki, Ralph; Loh, Nellie Y.; Górecki, Dariusz C.; Davies, Kay E.

doi:10.1073/pnas.95.1.241

Cited by 147 publications

(142 citation statements)

References 37 publications

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“…We showed here that decreased expression of Dp71 in the antisense-Dp71cells correlated with altered protein levels of dystrobrevins, while protein expression of h-dystrobrevin increased that of α−dystrobrevin showed a reduction. These results suggest that two alternative dystrobrevin-containing DAPC are present in PC12 cells, as previously observed in several tissues [6,32], and that Dp71 is necessary for the stability of the a-dystrobrevin-containing DAPC. Consistent with this interpretation, we have found by immunofluorescence assays that Dp71 and a-dystrobrevin distribute together in the cytoplasm and nucleus of PC12 cells (unpublished results).…”

Section: Discussionsupporting

confidence: 71%

Dystrophin Dp71 is required for neurite outgrowth in PC12 cells

Acosta

2004

Experimental Cell Research

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:To determine the role of Dp71 in neuronal cells, we generated PC12 cell lines in which Dp71 protein levels were controlled by stable transfection with either antisense or sense constructs. Cells expressing the antisense Dp71 RNA (antisense-Dp71 cells) contained reduced amounts of the two endogenous Dp71 isoforms. Antisense-Dp71 cells exhibited a marked suppression of neurite outgrowth upon the induction with NGF or dibutyryl cyclic AMP. Early responses to NGF-induced neuronal differentiation, such as the cessation of cell division and the activation of ERK1/2 proteins, were normal in the antisense-Dp71 cells. On contrary, the induction of MAP2, a late differentiation marker, was disturbed in these cells. Additionally, the deficiency of Dp71 correlated with an altered expression of the dystrophin-associated protein complex (DAPC) members a and h dystrobrevins. Our results indicate that normal expression of Dp71 is essential for neurite outgrowth in PC12 cells and constitute the first direct evidence implicating Dp71 in a neuronal function. D 2004 Elsevier Inc. All rights reserved.

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Section: Discussionsupporting

confidence: 71%

Dystrophin Dp71 is required for neurite outgrowth in PC12 cells

Acosta

2004

Experimental Cell Research

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“…In this context, the associations between dysbindin SNPs and cognitive domains in schizophrenia are noteworthy, as cognitive deficits are classical features of Duchenne's muscular dystrophy; interestingly, this disease also has a neuropathology reminiscent of schizophrenia, with a fronto-temporal distribution, cortical heterotopias, and reduced dendritic arborization of pyramidal neurons. 235 Since the DPC is concentrated at the postsynaptic density (PSD), 236 dysbindin is thought be involved in one or more PSD functions, which include trafficking and tethering of receptors (including NMDA, nicotinic, and GABA A receptors) and signal transduction proteins. 237,238 However, a substantial fraction of dysbindin occurs presynaptically.…”

Section: Dysbindin (Dtnbp1)mentioning

confidence: 99%

Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence

2004

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This review critically summarizes the neuropathology and genetics of schizophrenia, the relationship between them, and speculates on their functional convergence. The morphological correlates of schizophrenia are subtle, and range from a slight reduction in brain size to localized alterations in the morphology and molecular composition of specific neuronal, synaptic, and glial populations in the hippocampus, dorsolateral prefrontal cortex, and dorsal thalamus. These findings have fostered the view of schizophrenia as a disorder of connectivity and of the synapse. Although attractive, such concepts are vague, and differentiating primary events from epiphenomena has been difficult. A way forward is provided by the recent identification of several putative susceptibility genes (including neuregulin, dysbindin, COMT, DISC1, RGS4, GRM3, and G72). We discuss the evidence for these and other genes, along with what is known of their expression profiles and biological roles in brain and how these may be altered in schizophrenia. The evidence for several of the genes is now strong. However, for none, with the likely exception of COMT, has a causative allele or the mechanism by which it predisposes to schizophrenia been identified. Nevertheless, we speculate that the genes may all converge functionally upon schizophrenia risk via an influence upon synaptic plasticity and the development and stabilization of cortical microcircuitry. NMDA receptor-mediated glutamate transmission may be especially implicated, though there are also direct and indirect links to dopamine and GABA signalling. Hence, there is a correspondence between the putative roles of the genes at the molecular and synaptic levels and the existing understanding of the disorder at the neural systems level. Characterization of a core molecular pathway and a 'genetic cytoarchitecture' would be a profound advance in understanding schizophrenia, and may have equally significant therapeutic implications. Molecular Psychiatry (2005) 10, 40-68.

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“…One obvious possibility is that dystrophin acts as part of a DGC in brain as it does in muscle. Indeed, several DGC proteins are present in central neurons and appear to interact in a manner similar to that seen in muscle (Peters et al, 1997;Blake et al, 1998Blake et al, , 1999Moukhles and Carbonetto, 2001;Neely et al, 2001;Zaccaria et al, 2001;Brunig et al, 2002;Levi et al, 2002). However, cerebral phenotypes of mutants in which the DGC is disrupted primarily reflect abnormalities in non-neuronal cells.…”

Section: Introductionmentioning

confidence: 99%

Cerebellar Synaptic Defects and Abnormal Motor Behavior in Mice Lacking α- and β-Dystrobrevin

Grady¹,

Wozniak²,

Ohlemiller³

et al. 2006

J. Neurosci.

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The dystrobrevins (␣DB and ␤DB) bind directly to dystrophin and are components of a transmembrane dystrophin-glycoprotein complex (DGC) that links the cytoskeleton to extracellular proteins in many tissues. We show here that ␣DB, ␤DB, and dystrophin are all concentrated at a discrete subset of inhibitory synapses on the somata and dendrites of cerebellar Purkinje cells. Dystrophin is depleted from these synapses in mice lacking both ␣DB and ␤DB, and DBs are depleted from these synapses in mice lacking dystrophin. In dystrophin mutants and ␣DB,␤DB double mutants, the size and number of GABA receptor clusters are decreased at cerebellar inhibitory synapses, and sensorimotor behaviors that reflect cerebellar function are perturbed. Synaptic and behavioral abnormalities are minimal in mice lacking either ␣DB or ␤DB. Together, our results show that the DGC is required for proper maturation and function of a subset of inhibitory synapses, that DB is a key component of this DGC, and that interference with this DGC leads to behavioral abnormalities. We suggest that motor deficits in muscular dystrophy patients, which are their cardinal symptoms, may reflect not only peripheral derangements but also CNS defects.

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β-dystrobrevin, a member of the dystrophin-related protein family

Cited by 147 publications

References 37 publications

Dystrophin Dp71 is required for neurite outgrowth in PC12 cells

Dystrophin Dp71 is required for neurite outgrowth in PC12 cells

Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence

Cerebellar Synaptic Defects and Abnormal Motor Behavior in Mice Lacking α- and β-Dystrobrevin

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