Mouse α1-Syntrophin Binding to Grb2:  Further Evidence of a Role for Syntrophin in Cell Signaling

Oak, Shilpa; Russo, Katia; Petrucci, Tamara C.; Jarrett, Harry W.

doi:10.1021/bi010490n

Cited by 70 publications

(61 citation statements)

References 39 publications

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“…In addition, an increasing number of cellular functions associated with these multiple protein complexes have been proposed, such as membrane stability, cellular signaling and force transduction [7,33,34]. The specific function of each DAPC seems to be determined by the cellular environment where it resides as well as by the unique combination of proteins that conforms the complex.…”

Section: Discussionmentioning

confidence: 99%

Characterization of a novel Dp71 dystrophin-associated protein complex (DAPC) present in the nucleus of HeLa cells: Members of the nuclear DAPC associate with the nuclear matrix

Fuentes-Mera

Rodríguez-Muñóz

González‐Ramírez

et al. 2006

Experimental Cell Research

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, et al.. Characterization of a novel Dp71 dystrophin-associated protein complex (DAPC) present in the nucleus of HeLa cells: members of the nuclear DAPC associate with the nuclear matrix.. Experimental Cell Research, Elsevier, 2006, 312 (16) ABSTRACT: Dystrophin is an essential component in the assembly and maintenance of the dystrophinassociated protein complex (DAPC), which includes members of the dystroglycan, syntrophin, sarcoglycan and dystrobrevin protein families. Distinctive complexes have been described in the cell membrane of different tissues and cultured cells. In this work, we report the identification and characterization of a novel DAPC present in the nuclei of HeLa cells, which contains dystrophin Dp71 as a key component. Using confocal microscopy and cell fractionation analyses, we found the presence of Dp71, β-sarcoglycan, β-dystroglycan, α-and β-syntrophin, α1-and β-dystrobrevin and nNOS in the nuclei of HeLa cells. Furthermore, we demonstrated by coimmunoprecipitation experiments that most of these proteins form a complex in the nuclear compartment. Next, we analyze the possible association of the nuclear DAPC with the nuclear matrix. We found the presence of Dp71, β-dystroglycan, nNOS, β-sarcoglycan, α/β syntrophin, α1-dystrobrevin and β-dystrobrevin in the nuclear matrix protein fractions and in situ nuclear matrix preparations from HeLa cells. Moreover, we found that Dp71, β-dystroglycan and β-dystrobrevin co-immunoprecipitated with the nuclear matrix proteins lamin B1 and actin. The association of members of the nuclear DAPC with the nuclear matrix indicates that they may work as scaffolding proteins involved in nuclear architecture.

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Section: Discussionmentioning

confidence: 99%

Characterization of a novel Dp71 dystrophin-associated protein complex (DAPC) present in the nucleus of HeLa cells: Members of the nuclear DAPC associate with the nuclear matrix

Fuentes-Mera

Rodríguez-Muñóz

González‐Ramírez

et al. 2006

Experimental Cell Research

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“…It was therefore of interest to evaluate the status of members of the dystrophin-glycoprotein complex in diabetic muscle fibres. In addition, Grb2, an adapter protein involved in signal transduction, was shown to directly interact with the dystrophin-associated dystroglycans and syntrophins (Yang et al, 1995;Oak et al, 2001). Glucose transport is also stimulated by skeletal muscle contraction involving nitric oxide and cGMP as signalling intermediates (Etgen et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Expression of the skeletal muscle dystrophin–dystroglycan complex and syntrophin-nitric oxide synthase complex is severely affected in the type 2 diabetic Goto–Kakizaki rat

Mulvey

Harno

Keenan

et al. 2005

European Journal of Cell Biology

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The inability of insulin to stimulate glucose metabolism in skeletal muscle fibres is a classic characteristic of type 2 diabetes. Using the non-obese Goto-Kakizaki rat as an established animal model of this type of diabetes, sucrose gradient centrifugation studies were performed and confirmed the abnormal subcellular location of the glucose transporter GLUT4. In addition, this analysis revealed an unexpected drastic reduction in the surface membrane marker b-dystroglycan, a dystrophin-associated glycoprotein. Based on this finding, a comprehensive immunoblotting survey was conducted which showed a dramatic decrease in the Dp427 isoform of dystrophin and the a/b-dystroglycan subcomplex, but not in laminin, sarcoglycans, dystrobrevin, and excitation-contraction-relaxation cycle elements. Thus, the backbone of the trans-sarcolemmal linkage between the extracellular matrix and the actin membrane cytoskeleton might be structurally impaired in diabetic fibres. Immunohistochemical studies revealed that the reduction in the dystrophin-dystroglycan complex does not induce obvious signs of muscle pathology, and is neither universal in all fibres, nor fibre-type specific. Most importantly, the expression of a-syntrophin and the syntrophinassociated neuronal isoform of nitric oxide synthase, nNOS, was demonstrated to be severely reduced in diabetic fibres. The loss of the dystrophin-dystroglycan complex and the syntrophin-nNOS complex in selected fibres suggests a weakening of the sarcolemma, abnormal signalling and probably a decreased cytoprotective mechanism in diabetes. Impaired anchoring of the cortical actin cytoskeleton via dystrophin might interfere with the proper recruitment of the glucose transporter to the surface membrane, following stimulation by insulin or muscle contraction. This may, at least partially, be responsible for the insulin resistance in diabetic skeletal muscles.

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“…Our studies have identified that Arhgef5 is also a phosphodependent α-dystrobrevin-1 ligand. Moreover, Grb2 binds to two other components of the DGC -syntrophin and dystroglycan (Oak et al, 2001;Yang et al, 1995); and Fyn interacts with AChRs, Grb2, PI3K and SH3BP2 (Foucault et al, 2005;Fuhrer and Hall, 1996;Gout et al, 1992;Kapeller et al, 1994;Li et al, 1996). Binding to multiple components is characteristic for proteins that have important functions in the organization of synaptic machinery and could explain α-catulin and Grb2 synaptic localization in α-dystrobrevin-KO tissues.…”

Section: Discussionmentioning

confidence: 99%

α-Dystrobrevin-1 recruits Grb2 and α-catulin to organize neurotransmitter receptors at the neuromuscular junction

Gingras

Gawor

Bernadzki

et al. 2016

Journal of Cell Science

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Neuromuscular junctions (NMJs), the synapses made by motor neurons on muscle fibers, form during embryonic development but undergo substantial remodeling postnatally. Several lines of evidence suggest that α-dystrobrevin, a component of the dystrophinassociated glycoprotein complex (DGC), is a crucial regulator of the remodeling process and that tyrosine phosphorylation of one isoform, α-dystrobrevin-1, is required for its function at synapses. We identified a functionally important phosphorylation site on α-dystrobrevin-1, generated phosphorylation-specific antibodies to it and used them to demonstrate dramatic increases in phosphorylation during the remodeling period, as well as in nerve-dependent regulation in adults. We then identified proteins that bind to this site in a phosphorylation-dependent manner and others that bind to α-dystrobrevin-1 in a phosphorylation-independent manner. They include multiple members of the DGC, as well as α-catulin, liprin-α1, Usp9x, PI3K, Arhgef5 and Grb2. Finally, we show that two interactors, α-catulin ( phosphorylation independent) and Grb2 ( phosphorylation dependent) are localized to NMJs in vivo, and that they are required for proper organization of neurotransmitter receptors on myotubes.

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Mouse α1-Syntrophin Binding to Grb2: Further Evidence of a Role for Syntrophin in Cell Signaling

Cited by 70 publications

References 39 publications

Characterization of a novel Dp71 dystrophin-associated protein complex (DAPC) present in the nucleus of HeLa cells: Members of the nuclear DAPC associate with the nuclear matrix

Characterization of a novel Dp71 dystrophin-associated protein complex (DAPC) present in the nucleus of HeLa cells: Members of the nuclear DAPC associate with the nuclear matrix

Expression of the skeletal muscle dystrophin–dystroglycan complex and syntrophin-nitric oxide synthase complex is severely affected in the type 2 diabetic Goto–Kakizaki rat

α-Dystrobrevin-1 recruits Grb2 and α-catulin to organize neurotransmitter receptors at the neuromuscular junction

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