β-Dystrobrevin, a new member of the dystrophin family: Identification, cloning, and protein associations

Harvard University, Cambridge, Massachusetts, United States
Journal of Biological Chemistry (Impact Factor: 4.57). 01/1998; 272(50):31561-9. DOI: 10.1074/jbc.272.50.31561
Source: PubMed


Dystrophin, the protein disrupted in Duchenne muscular dystrophy, is one of several related proteins that are key components of the submembrane cytoskeleton. Three dystrophin-related proteins (utrophin, dystrophin-related protein-2 (DRP2), and dystrobrevin) have been described. Here, we identify a human gene on chromosome 2p22-23 that encodes a novel protein, beta-dystrobrevin, with significant homology to the other known dystrobrevin (now termed alpha-dystrobrevin). Sequence alignments including this second dystrobrevin strongly support the concept that two distinct subfamilies exist within the dystrophin family, one composed of dystrophin, utrophin, and DRP2 and the other composed of alpha- and beta-dystrobrevin. The possibility that members of each subfamily form distinct protein complexes was examined by immunopurifying dystrobrevins and dystrophin. A beta-dystrobrevin antibody recognized a protein of the predicted size (71 kDa) that copurified with the dystrophin short form, Dp71. Thus, like alpha-dystrobrevin, beta-dystrobrevin is likely to associate directly with dystrophin. alpha- and beta-dystrobrevins failed to copurify with each other, however. These results suggest that members of the dystrobrevin subfamily form heterotypic associations with dystrophin and raise the possibility that pairing of a particular dystrobrevin with dystrophin may be regulated, thereby providing a mechanism for assembly of distinct submembrane protein complexes.

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Available from: Stan Froehner, Aug 28, 2015
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    • "The mammalian dystrobrevin protein family is comprised of α- and β-dystrobrevin which are encoded by the DTNA and DTNB gene, respectively [4,12]. α-Dystrobrevin is expressed predominantly in muscle and brain whereas β-dystrobrevin is expressed in non-muscle tissues [3,4,12]. "
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    ABSTRACT: Muscular dystrophies are a group of diseases that primarily affect striated muscle and are characterized by the progressive loss of muscle strength and integrity. Major forms of muscular dystrophies are caused by the abnormalities of the dystrophin glycoprotein complex (DGC) that plays crucial roles as a structural unit and scaffolds for signaling molecules at the sarcolemma. α-Dystrobrevin is a component of the DGC and directly associates with dystrophin. α-Dystrobrevin also binds to intermediate filaments as well as syntrophin, a modular adaptor protein thought to be involved in signaling. Although no muscular dystrophy has been associated within mutations of the α-dystrobrevin gene, emerging findings suggest potential significance of α-dystrobrevin in striated muscle. This review addresses the functional role of α-dystrobrevin in muscle as well as its possible implication for muscular dystrophy.
    International Journal of Molecular Sciences 12/2011; 12(3):1660-71. DOI:10.3390/ijms12031660 · 2.86 Impact Factor
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    • "Syntrophins and dystrobrevins are the cytoplasmic components of DAGs [43]. Syntrophins contain α, β1, β2, γ1, and γ2 isoforms which have been characterized so far [53] [54]; while dystrobrevins have α (−1 ∼ −5) and βisoforms [55] [56] [57] [58]. Alternative splicing yields five forms of αdystrobrevin , of which two predominate in skeletal muscle: full-length α-dystrobrevin-1 (84 kDa), and C-terminal truncated α-dystrobrevin-2 (65 kDa) [57]. "
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    ABSTRACT: Freeze-fracture electron microscopy enabled us to observe the molecular architecture of the biological membranes. We were studying the myofiber plasma membranes of health and disease by using this technique and were interested in the special assembly called orthogonal arrays (OAs). OAs were present in normal myofiber plasma membranes and were especially numerous in fast twitch type 2 myofibers; while OAs were lost from sarcolemmal plasma membranes of severely affected muscles with dystrophinopathy and dysferlinopathy but not with caveolinopathy. In the mid nineties of the last century, the OAs turned out to be a water channel named aquaporin 4 (AQP4). Since this discovery, several groups of investigators have been studying AQP4 expression in diseased muscles. This review summarizes the papers which describe the expression of OAs, AQP4, and other AQPs at the sarcolemma of healthy and diseased muscle and discusses the possible role of AQPs, especially that of AQP4, in normal and pathological skeletal muscles.
    BioMed Research International 03/2010; 2010:731569. DOI:10.1155/2010/731569 · 2.71 Impact Factor
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    • "We recently demonstrated that the diversity of expression of the Dystrophin associated protein complex (DAPC) plays a key role in the platelet haemostatic functions, participating as a membrane scaffold as well as having a signalling role (Cerecedo et al, 2005, 2006a). Dystrobrevins are cytoplasmic components of the DAPC that link the actin cytoskeleton to the extracellular matrix in skeletal muscle (Blake et al, 2002); they are the product of two different genes coding for two highly similar proteins, i.e. a-and b-dystrobrevin (Ambrose et al, 1997; Peters et al, 1997; Blake et al, 1998). Dystrobrevins have been characterized in association with dystrophin isoforms and utrophin in several non-muscle tissues including platelets (Cerecedo et al, 2005). "
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    ABSTRACT: Upon activation with physiological stimuli, human platelets undergo morphological changes, centralizing their organelles and secreting effector molecules at the site of vascular injury. Previous studies have indicated that the actin filaments and microtubules of suspension-activated platelets play a critical role in granule movement and exocytosis; however, the participation of these cytoskeleton elements in adhered platelets remains unexplored. alpha- and beta-dystrobrevin members of the dystrophin-associated protein complex in muscle and non-muscle cells have been described as motor protein receptors that might participate in the transport of cellular components in neurons. Recently, we characterized the expression of dystrobrevins in platelets; however, their functional diversity within this cellular model had not been elucidated. The present study examined the contribution of actin filaments and microtubules in granule trafficking during the platelet adhesion process using cytoskeleton-disrupting drugs, quantification of soluble P-selectin, fluorescence resonance transfer energy analysis and immunoprecipitation assays. Likewise, we assessed the interaction of alpha-dystrobrevins with the ubiquitous kinesin heavy chain. Our results strongly suggest that microtubules and actin filaments participate in the transport of alpha and dense granules in the platelet adhesion process, during which alpha-dystrobrevins play the role of regulatory and adaptor proteins that govern trafficking events.
    British Journal of Haematology 02/2010; 149(1):124-36. DOI:10.1111/j.1365-2141.2010.08085.x · 4.71 Impact Factor
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