Differential Membrane Localization and Intermolecular Associations of α-Dystrobrevin Isoforms in Skeletal Muscle

Peters, Matthew F.; Puccio, Hélène; Grady, R. Mark; Kramarcy, Neal R.; Kunkel, Louis M.; Sanes, Joshua R.; Sealock, Robert; Froehner, Stanley C.

doi:10.1083/jcb.142.5.1269

Cited by 112 publications

(126 citation statements)

References 44 publications

(139 reference statements)

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“…Antibodies generated against α-DB1, α-DB2, β-DB, pan-DB, utrophin, and syntrophin were described previously (42)(43)(44). Other antibodies were purchased from commercial sources: anti-dystrophin and anti-flag (Sigma), anti-HA (Cell Signaling), and anti-α-catulin (Abnova).…”

Section: Methodsmentioning

confidence: 99%

α-Dystrobrevin-1 recruits α-catulin to the α _1D -adrenergic receptor/dystrophin-associated protein complex signalosome

Lyssand¹,

Whiting

Lee³

et al. 2010

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

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α 1D -Adrenergic receptors (ARs) are key regulators of cardiovascular system function that increase blood pressure and promote vascular remodeling. Unfortunately, little information exists about the signaling pathways used by this important G protein-coupled receptor (GPCR). We recently discovered that α 1D -ARs form a “signalosome” with multiple members of the dystrophin-associated protein complex (DAPC) to become functionally expressed at the plasma membrane and bind ligands. However, the molecular mechanism by which the DAPC imparts functionality to the α 1D -AR signalosome remains a mystery. To test the hypothesis that previously unidentified molecules are recruited to the α 1D -AR signalosome, we performed an extensive proteomic analysis on each member of the DAPC. Bioinformatic analysis of our proteomic data sets detected a common interacting protein of relatively unknown function, α-catulin. Coimmunoprecipitation and blot overlay assays indicate that α-catulin is directly recruited to the α 1D -AR signalosome by the C-terminal domain of α-dystrobrevin-1 and not the closely related splice variant α-dystrobrevin-2. Proteomic and biochemical analysis revealed that α-catulin supersensitizes α 1D -AR functional responses by recruiting effector molecules to the signalosome. Taken together, our study implicates α-catulin as a unique regulator of GPCR signaling and represents a unique expansion of the intricate and continually evolving array of GPCR signaling networks.

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Section: Methodsmentioning

confidence: 99%

α-Dystrobrevin-1 recruits α-catulin to the α _1D -adrenergic receptor/dystrophin-associated protein complex signalosome

Lyssand¹,

Whiting

Lee³

et al. 2010

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

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“…We have previously characterized the following antibodies: pan-specific syntrophin monoclonal antibody (mAb) SYN1351 (Froehner et al, 1987); isoform specific syntrophin polyclonal antibodies (pAbs) SYN17 (␣-syntrophin), SYN28 (␤2-syntrophin), and SYN37 (␤1-syntrophin) (Peters et al, 1997); pAb 1862 (utrophin) ; pAb 2723 (C terminus of dystrophin) ; dystrobrevin Abs 638 (␣-dystrobrevin-1), and D〉2 (␣-dystrobrevin-2) (Peters et al, 1998). The sodium channel antibody was a gift from S. Rock Levinson (University of Colorado Health Sciences Center).…”

Section: Methodsmentioning

confidence: 99%

“…Immunofluorescence labeling of cross sections was performed on unfixed quadriceps muscle using 8 m cryosections as described (Peters et al, 1998).…”

Section: Methodsmentioning

confidence: 99%

Structural Abnormalities at Neuromuscular Synapses Lacking Multiple Syntrophin Isoforms

Adams¹,

Kramarcy²,

Fukuda³

et al. 2004

J. Neurosci.

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The syntrophins are modular adapter proteins that function by recruiting signaling molecules to the cytoskeleton via their direct association with proteins of the dystrophin protein family. We investigated the physiological function of ␤2-syntrophin by generating a line of mice lacking this syntrophin isoform. The ␤2-syntrophin null mice show no overt phenotype, or muscular dystrophy, and form structurally normal neuromuscular junctions (NMJs). To determine whether physiological consequences caused by the lack of ␤2-syntrophin were masked by compensation from the ␣-syntrophin isoform, we crossed these mice with our previously described ␣-syntrophin null mice to produce mice lacking both isoforms. The ␣/␤2-syntrophin null mice have NMJs that are structurally more aberrant than those lacking only ␣-syntrophin. The NMJs of the ␣/␤2-syntrophin null mice have fewer junctional folds than either parent strain, and the remaining folds are abnormally shaped with few openings to the synaptic space. The levels of acetylcholine receptors are reduced to 23% of wild type in mice lacking both syntrophin isoforms. Furthermore, the ␣/␤2-syntrophin null mice ran significantly shorter distances on voluntary exercise wheels despite having normal neuromuscular junction transmission as determined by microelectrode recording of endplate potentials. We conclude that both ␣-syntrophin and ␤2-syntrophin play distinct roles in forming and maintaining NMJ structure and that each syntrophin can partially compensate for the loss of the other.

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“…8A) where both ␣-dystrobrevin-1 and -2 are concentrated (40,42). Here, DAMAGE appears not to colocalize with acetylcholine receptors but instead occupies a submembrane compartment directly beneath the synapse (Fig.…”

Section: ␣-Dystrobrevin Interaction With Damage/mage-e1mentioning

confidence: 99%

DAMAGE, a Novel α-Dystrobrevin-associated MAGE Protein in Dystrophin Complexes

Albrecht

Froehner

2004

Journal of Biological Chemistry

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Mice rendered null for ␣-dystrobrevin, a component of the dystrophin complex, have muscular dystrophy, despite the fact that the sarcolemma remains relatively intact (Grady, R. M., Grange, R. W., Lau, K. S., Maimone, M. M., Nichol, M. C., Stull, J. T., and Sanes, J. R. (1999) Nat. Cell Biol. 1, 215-220) Thus, ␣-dystrobrevin may serve a signaling function that is important for the maintenance of muscle integrity. We have identified a new dystrobrevin-associated protein, DAMAGE, that may play a signaling role in brain, muscle, and peripheral nerve. In humans, DAMAGE is encoded by an intronless gene located at chromosome Xq13.1, a locus that contains genes involved in mental retardation. DAM-AGE associates directly with ␣-dystrobrevin, as shown by yeast two-hybrid, and co-immunoprecipitates with the dystrobrevin-syntrophin complex from brain. This co-immunoprecipitation is dependent on the presence of ␣-dystrobrevin but not ␤-dystrobrevin. The DAMAGE protein contains a potential nuclear localization signal, 30 12-amino acid repeats, and two MAGE homology domains. The domain structure of DAMAGE is similar to that of NRAGE, a MAGE protein that mediates p75 neurotrophin receptor signaling and neuronal apoptosis (Salehi, A. H., Roux, P. P., Kubu, C. J., Zeindler, C., Bhakar, A., Tannis, L. L., Verdi, J. M., and Barker, P. A. (2000) Neuron 27, 279 -288). DAMAGE is highly expressed in brain and is present in the cell bodies and dendrites of hippocampal and Purkinje neurons. In skeletal muscle, DAMAGE is at the postsynaptic membrane and is associated with a subset of myonuclei. DAMAGE is also expressed in peripheral nerve, where it localizes along with other members of the dystrophin complex to the perineurium and myelin. These results expand the role of dystrobrevin and the dystrophin complex in membrane signaling and disease.The dystrophin glycoprotein complex links the actin cytoskeleton to the extracellular matrix in skeletal muscle. In addition, recent studies (1-7) have shown that the dystrophin complex is critical for the localization of a variety of signaling molecules to the skeletal muscle sarcolemma. Thus, the dystrophin complex functions as both a structural link to the extracellular matrix and as a scaffold that concentrates and stabilizes functionally inter-related signaling proteins at the muscle cell membrane.Part of the signaling function of the dystrophin complex may be mediated by the dystrobrevins. The role of the dystrobrevins in signaling is not fully understood; however, targeted disruption of the ␣-dystrobrevin gene in mice results in muscle pathology without the membrane fragility characteristic of dystrophin-deficient muscular dystrophy (8). These findings suggest that ␣-dystrobrevin is important for muscle function but in a non-structural way. Dystrobrevin has no enzymatic activity of its own; therefore, the involvement of dystrobrevin in signaling pathways is dependent on its interaction with other proteins.The dystrobrevins are transcribed from two separate genes, designated ␣ and ␤, that shar...

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Differential Membrane Localization and Intermolecular Associations of α-Dystrobrevin Isoforms in Skeletal Muscle

Cited by 112 publications

References 44 publications

α-Dystrobrevin-1 recruits α-catulin to the α _1D -adrenergic receptor/dystrophin-associated protein complex signalosome

α-Dystrobrevin-1 recruits α-catulin to the α _1D -adrenergic receptor/dystrophin-associated protein complex signalosome

Structural Abnormalities at Neuromuscular Synapses Lacking Multiple Syntrophin Isoforms

DAMAGE, a Novel α-Dystrobrevin-associated MAGE Protein in Dystrophin Complexes

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Differential Membrane Localization and Intermolecular Associations of α-Dystrobrevin Isoforms in Skeletal Muscle

Cited by 112 publications

References 44 publications

α-Dystrobrevin-1 recruits α-catulin to the α 1D -adrenergic receptor/dystrophin-associated protein complex signalosome

α-Dystrobrevin-1 recruits α-catulin to the α 1D -adrenergic receptor/dystrophin-associated protein complex signalosome

Structural Abnormalities at Neuromuscular Synapses Lacking Multiple Syntrophin Isoforms

DAMAGE, a Novel α-Dystrobrevin-associated MAGE Protein in Dystrophin Complexes

Contact Info

Product

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α-Dystrobrevin-1 recruits α-catulin to the α _1D -adrenergic receptor/dystrophin-associated protein complex signalosome

α-Dystrobrevin-1 recruits α-catulin to the α _1D -adrenergic receptor/dystrophin-associated protein complex signalosome