Utrophin-dystroglycan complex in membranes of adherent cultured cells.

In skeletal muscle, dystrophin binds to an oligomeric, transmembrane complex (DAGc; dystrophin-associated glycoprotein complex) which interacts with laminin in the extracellular matrix. We now present biochemical evidence for an association between utrophin (dystrophin-related protein, DRP) and a major DAGc component, beta-dystroglycan (43DAG) in cultured cell lines which contain little if any dystrophin. We have shown also that utrophin and beta-dystroglycan co-localise at or near the plasma membrane and that they co-sediment in large complexes on sucrose density gradients. On the lower plasma membrane, in contact with the substratum, part of the utrophin and beta-dystroglycan staining co-localised with alpha-actinin in a punctate distribution outside classical vinculin-rich focal adhesions. beta-dystroglycan, utrophin, syntrophin (59DAP), and alpha-actinin were found in all adhesion-competent cell lines studied, but levels of the last three proteins were greatly reduced in myeloma cells, which cannot readily attach to substrata. Possible roles for utrophin in cultured cells are considered in the light of recent evidence for involvement of utrophin-glycoprotein complexes in muscle in signal transduction and recruitment of acetylcholine receptors to neuromuscular junctions.

[1]  K. Burridge,et al.  Association of Aciculin with Dystrophin and Utrophin (*) , 1995, The Journal of Biological Chemistry.

[2]  Simon C Watkins,et al.  Interaction of chromosome-6-encoded dystrophin related protein with the extracellular matrix. , 1995, Journal of cell science.

[3]  K. Davies,et al.  Utrophin actin binding domain: analysis of actin binding and cellular targeting. , 1995, Journal of cell science.

[4]  B. André,et al.  WWP, a new amino acid motif present in single or multiple copies in various proteins including dystrophin and the SH3-binding Yes-associated protein YAP65. , 1994, Biochemical and biophysical research communications.

[5]  Z. Hall,et al.  Dystroglycan binds nerve and muscle agrin , 1994, Neuron.

[6]  S. Barry,et al.  The RhoA-dependent assembly of focal adhesions in Swiss 3T3 cells is associated with increased tyrosine phosphorylation and the recruitment of both pp125FAK and protein kinase C-delta to focal adhesions. , 1994, Journal of cell science.

[7]  K. Burridge,et al.  Expression and localization of the phosphoglucomutase-related cytoskeletal protein, aciculin, in skeletal muscle. , 1994, Journal of cell science.

[8]  S. Froehner,et al.  Dystrophin-associated proteins and synapse formation: Is α-dystroglycan the agrin receptor? , 1994, Cell.

[9]  S. Carbonetto,et al.  Dystroglycan-α, a dystrophin-associated glycoprotein, is a functional agrin receptor , 1994, Cell.

[10]  K. Campbell,et al.  A role for dystrophin-associated glycoproteins and utrophin in agrin-induced AChR clustering , 1994, Cell.

[11]  J. Leszyk,et al.  Identification and purification of an agrin receptor from torpedo postsynaptic membranes: A heteromeric complex related to the dystroglycans , 1994, Neuron.

[12]  C. Otey,et al.  Role of Adhesion Molecule Cytoplasmic Domains in Mediating Interactions with the Cytoskeleton , 1994, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[13]  Kensuke Hayashi,et al.  Molecular organization at the glycoprotein-complex-binding site of dystrophin. Three dystrophin-associated proteins bind directly to the carboxy-terminal portion of dystrophin. , 1994, European journal of biochemistry.

[14]  T. Helliwell,et al.  Expression of the 43 kDa dystrophin-associated glycoprotein in human neuromuscular disease , 1994, Neuromuscular Disorders.

[15]  S. Webb,et al.  Synthesis and cell-adhesion properties of cyclo(-Arg-Gly-Asp-Ser-Lys-), a constrained analogue of the active domain of fibronectin , 1994 .

[16]  K. Campbell,et al.  Differential expression of dystrophin, utrophin and dystrophin‐associated proteins in peripheral nerve , 1993, FEBS letters.

[17]  K. Campbell,et al.  Clustering and immobilization of acetylcholine receptors by the 43-kD protein: a possible role for dystrophin-related protein , 1993, The Journal of cell biology.

[18]  M. F. Peters,et al.  Two forms of mouse syntrophin, a 58 kd dystrophin-associated protein, differ in primary structure and tissue distribution , 1993, Neuron.

[19]  J. Ellis,et al.  A quantitative ELISA for dystrophin. , 1993, Journal of immunological methods.

[20]  J. Small,et al.  Complementary distributions of vinculin and dystrophin define two distinct sarcolemma domains in smooth muscle , 1993, The Journal of cell biology.

[21]  M. Takemitsu,et al.  Immunoblot analysis of dystrophin-related protein (DRP). , 1993, Biochimica et biophysica acta.

[22]  J. Ervasti,et al.  Association of dystrophin-related protein with dystrophin-associated proteins in mdx mouse muscle , 1992, Nature.

[23]  F. Walsh,et al.  Co-localization and molecular association of dystrophin with laminin at the surface of mouse and human myotubes. , 1992, Journal of cell science.

[24]  K. Davies,et al.  Utrophin, the autosomal homologue of dystrophin, is widely‐expressed and membrane‐associated in cultured cell lines , 1992, FEBS letters.

[25]  Z. Levy,et al.  A 71-kilodalton protein is a major product of the Duchenne muscular dystrophy gene in brain and other nonmuscle tissues. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Richard O. Hynes,et al.  Integrins: Versatility, modulation, and signaling in cell adhesion , 1992, Cell.

[27]  O. Ibraghimov-Beskrovnaya,et al.  Primary structure of dystrophin-associated glycoproteins linking dystrophin to the extracellular matrix , 1992, Nature.

[28]  K. Davies,et al.  Localization of the DMDL gene-encoded dystrophin-related protein using a panel of nineteen monoclonal antibodies: presence at neuromuscular junctions, in the sarcolemma of dystrophic skeletal muscle, in vascular and other smooth muscles, and in proliferating brain cell lines , 1991, The Journal of cell biology.

[29]  J. Ervasti,et al.  Membrane organization of the dystrophin-glycoprotein complex , 1991, Cell.

[30]  P. Barr,et al.  Mammalian subtilisins: The long-sought dibasic processing endoproteases , 1991, Cell.

[31]  J. Ervasti,et al.  Dystrophin-glycoprotein complex is highly enriched in isolated skeletal muscle sarcolemma , 1991, The Journal of cell biology.

[32]  R. Sealock,et al.  Dystrophin as a focal adhesion protein , 1990, FEBS letters.

[33]  E. Ozawa,et al.  Glycoprotein complex anchoring dystrophin to sarcolemma. , 1990, Journal of biochemistry.

[34]  L. Kunkel,et al.  Identification of a chromosome 6-encoded dystrophin-related protein. , 1990, The Journal of biological chemistry.

[35]  J. Ervasti,et al.  Deficiency of a glycoprotein component of the dystrophin complex in dystrophic muscle , 1990, Nature.

[36]  K. Davies,et al.  Monoclonal antibodies against defined regions of the muscular dystrophy protein, dystrophin , 1990, FEBS letters.

[37]  G. Jones.  Establishment, maintenance, and cloning of human primary cell strains. , 1990, Methods in molecular biology.

[38]  D. Hill,et al.  An autosomal transcript in skeletal muscle with homology to dystrophin , 1989, Nature.

[39]  K. Campbell,et al.  Association of dystrophin and an integral membrane glycoprotein , 1989, Nature.

[40]  B. Geiger.  Cytoskeleton-associated cell contacts. , 1989, Current opinion in cell biology.

[41]  C. Turner,et al.  Focal adhesions: transmembrane junctions between the extracellular matrix and the cytoskeleton. , 1988, Annual review of cell biology.

[42]  Eric P. Hoffman,et al.  Dystrophin: The protein product of the duchenne muscular dystrophy locus , 1987, Cell.

[43]  H. Peng,et al.  A postsynaptic Mr 58,000 (58K) protein concentrated at acetylcholine receptor-rich sites in Torpedo electroplaques and skeletal muscle , 1987, The Journal of cell biology.

[44]  ARCH. Geikie.  Lehrbuch der Mineralien und Felsartenkunde , 1871, Nature.