J. Cell Biol.
© The Rockefeller University Press
0021-9525/97/07/81/13 $2.00
Volume 138, Number 1, July 14, 1997 81-93

Differential Association of Syntrophin Pairs with the Dystrophin Complex

Matthew F. Peters, Marvin E. Adams, and Stanley C. Froehner

Department of Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7545

The syntrophins are a multigene family of intracellular dystrophin-associated proteins comprising three isoforms, 1, 1, and 2. Based on their domain organization and association with neuronal nitric oxide synthase, syntrophins are thought to function as modular adapters that recruit signaling proteins to the membrane via association with the dystrophin complex. Using sequences derived from a new mouse 1-syntrophin cDNA, and previously isolated cDNAs for 1- and 2-syntrophins, we prepared isoform-specific antibodies to study the expression, skeletal muscle localization, and dystrophin family association of all three syntrophins. Most tissues express multiple syntrophin isoforms. In mouse gastrocnemius skeletal muscle, 1- and 1-syntrophin are concentrated at the neuromuscular junction but are also present on the extrasynaptic sarcolemma. 1-syntrophin is restricted to fast-twitch muscle fibers, the first fibers to degenerate in Duchenne muscular dystrophy. 2-syntrophin is largely restricted to the neuromuscular junction.

The sarcolemmal distribution of 1- and 1-syntrophins suggests association with dystrophin and dystrobrevin, whereas all three syntrophins could potentially associate with utrophin at the neuromuscular junction. Utrophin complexes immunoisolated from skeletal muscle are highly enriched in 1- and 2-syntrophins, while dystrophin complexes contain mostly 1- and 1-syntrophins. Dystrobrevin complexes contain dystrophin and 1- and 1-syntrophins. From these results, we propose a model in which a dystrophin-dystrobrevin complex is associated with two syntrophins. Since individual syntrophins do not have intrinsic binding specificity for dystrophin, dystrobrevin, or utrophin, the observed preferential pairing of syntrophins must depend on extrinsic regulatory mechanisms.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Li, D., Long, C., Yue, Y., Duan, D. (2009). Sub-physiological sarcoglycan expression contributes to compensatory muscle protection in mdx mice. Hum Mol Genet 18: 1209-1220 [Abstract] [Full Text]  
• Lyssand, J. S., DeFino, M. C., Tang, X.-b., Hertz, A. L., Feller, D. B., Wacker, J. L., Adams, M. E., Hague, C. (2008). Blood Pressure Is Regulated by an {alpha}1D-Adrenergic Receptor/Dystrophin Signalosome. J. Biol. Chem. 283: 18792-18800 [Abstract] [Full Text]  
• Adams, M. E., Tesch, Y., Percival, J. M., Albrecht, D. E., Conhaim, J. I., Anderson, K., Froehner, S. C. (2008). Differential targeting of nNOS and AQP4 to dystrophin-deficient sarcolemma by membrane-directed {alpha}-dystrobrevin. J. Cell Sci. 121: 48-54 [Abstract] [Full Text]  
• Vandebrouck, A., Sabourin, J., Rivet, J., Balghi, H., Sebille, S., Kitzis, A., Raymond, G., Cognard, C., Bourmeyster, N., Constantin, B. (2007). Regulation of capacitative calcium entries by {alpha}1-syntrophin: association of TRPC1 with dystrophin complex and the PDZ domain of {alpha}1-syntrophin. FASEB J. 21: 608-617 [Abstract] [Full Text]  
• Frydenlund, D. S., Bhardwaj, A., Otsuka, T., Mylonakou, M. N., Yasumura, T., Davidson, K. G. V., Zeynalov, E., Skare, O., Laake, P., Haug, F.-M., Rash, J. E., Agre, P., Ottersen, O. P., Amiry-Moghaddam, M. (2006). Temporary loss of perivascular aquaporin-4 in neocortex after transient middle cerebral artery occlusion in mice. Proc. Natl. Acad. Sci. USA 103: 13532-13536 [Abstract] [Full Text]  
• Williams, J. C., Armesilla, A. L., Mohamed, T. M. A., Hagarty, C. L., McIntyre, F. H., Schomburg, S., Zaki, A. O., Oceandy, D., Cartwright, E. J., Buch, M. H., Emerson, M., Neyses, L. (2006). The Sarcolemmal Calcium Pump, {alpha}-1 Syntrophin, and Neuronal Nitric-oxide Synthase Are Parts of a Macromolecular Protein Complex. J. Biol. Chem. 281: 23341-23348 [Abstract] [Full Text]  
• Slater, C. R., Fawcett, P. R. W., Walls, T. J., Lyons, P. R., Bailey, S. J., Beeson, D., Young, C., Gardner-Medwin, D. (2006). Pre- and post-synaptic abnormalities associated with impaired neuromuscular transmission in a group of patients with 'limb-girdle myasthenia'.. Brain 129: 2061-2076 [Abstract] [Full Text]  
• Mercado, M. L., Amenta, A. R., Hagiwara, H., Rafii, M. S., Lechner, B. E., Owens, R. T., McQuillan, D. J., Froehner, S. C., Fallon, J. R. (2006). Biglycan regulates the expression and sarcolemmal localization of dystrobrevin, syntrophin, and nNOS. FASEB J. 20: 1724-1726 [Abstract] [Full Text]  
• Li, S., Kimura, E., Ng, R., Fall, B. M., Meuse, L., Reyes, M., Faulkner, J. A., Chamberlain, J. S. (2006). A highly functional mini-dystrophin/GFP fusion gene for cell and gene therapy studies of Duchenne muscular dystrophy. Hum Mol Genet 15: 1610-1622 [Abstract] [Full Text]  
• Chen, Z., Hague, C., Hall, R. A., Minneman, K. P. (2006). Syntrophins Regulate {alpha}1D-Adrenergic Receptors through a PDZ Domain-mediated Interaction. J. Biol. Chem. 281: 12414-12420 [Abstract] [Full Text]  
• Judge, L. M., Haraguchiln, M., Chamberlain, J. S. (2006). Dissecting the signaling and mechanical functions of the dystrophin-glycoprotein complex. J. Cell Sci. 119: 1537-1546 [Abstract] [Full Text]  
• Okuhira, K.-i., Fitzgerald, M. L., Sarracino, D. A., Manning, J. J., Bell, S. A., Goss, J. L., Freeman, M. W. (2005). Purification of ATP-binding Cassette Transporter A1 and Associated Binding Proteins Reveals the Importance of {beta}1-Syntrophin in Cholesterol Efflux. J. Biol. Chem. 280: 39653-39664 [Abstract] [Full Text]  
• Luo, S., Chen, Y., Lai, K.-O., Arevalo, J. C., Froehner, S. C., Adams, M. E., Chao, M. V., Ip, N. Y. (2005). {alpha}-Syntrophin regulates ARMS localization at the neuromuscular junction and enhances EphA4 signaling in an ARMS-dependent manner. JCB 169: 813-824 [Abstract] [Full Text]  
• Hogan, A., Yakubchyk, Y., Chabot, J., Obagi, C., Daher, E., Maekawa, K., Gee, S. H. (2004). The Phosphoinositol 3,4-Bisphosphate-binding Protein TAPP1 Interacts with Syntrophins and Regulates Actin Cytoskeletal Organization. J. Biol. Chem. 279: 53717-53724 [Abstract] [Full Text]  
• Adams, M. E., Kramarcy, N., Fukuda, T., Engel, A. G., Sealock, R., Froehner, S. C. (2004). Structural Abnormalities at Neuromuscular Synapses Lacking Multiple Syntrophin Isoforms. J. Neurosci. 24: 10302-10309 [Abstract] [Full Text]  
• Leonoudakis, D., Conti, L. R., Anderson, S., Radeke, C. M., McGuire, L. M. M., Adams, M. E., Froehner, S. C., Yates, J. R. III, Vandenberg, C. A. (2004). Protein Trafficking and Anchoring Complexes Revealed by Proteomic Analysis of Inward Rectifier Potassium Channel (Kir2.x)-associated Proteins. J. Biol. Chem. 279: 22331-22346 [Abstract] [Full Text]  
• Munehira, Y., Ohnishi, T., Kawamoto, S., Furuya, A., Shitara, K., Imamura, M., Yokota, T., Takeda, S., Amachi, T., Matsuo, M., Kioka, N., Ueda, K. (2004). {alpha}1-Syntrophin Modulates Turnover of ABCA1. J. Biol. Chem. 279: 15091-15095 [Abstract] [Full Text]  
• Albrecht, D. E., Froehner, S. C. (2004). DAMAGE, a Novel {alpha}-Dystrobrevin-associated MAGE Protein in Dystrophin Complexes. J. Biol. Chem. 279: 7014-7023 [Abstract] [Full Text]  
• Macioce, P., Gambara, G., Bernassola, M., Gaddini, L., Torreri, P., Macchia, G., Ramoni, C., Ceccarini, M., Petrucci, T. C. (2003). {beta}-Dystrobrevin interacts directly with kinesin heavy chain in brain. J. Cell Sci. 116: 4847-4856 [Abstract] [Full Text]  
• Abramovici, H., Hogan, A. B., Obagi, C., Topham, M. K., Gee, S. H. (2003). Diacylglycerol Kinase-{zeta} Localization in Skeletal Muscle Is Regulated by Phosphorylation and Interaction with Syntrophins. Mol. Biol. Cell 14: 4499-4511 [Abstract] [Full Text]  
• Martin, P. T. (2003). Dystroglycan glycosylation and its role in matrix binding in skeletal muscle. Glycobiology 13: 55R-66R [Abstract] [Full Text]  
• Khanna, S., Richmonds, C. R., Kaminski, H. J., Porter, J. D. (2003). Molecular Organization of the Extraocular Muscle Neuromuscular Junction: Partial Conservation of and Divergence from the Skeletal Muscle Prototype. IOVS 44: 1918-1926 [Abstract] [Full Text]  
• Michele, D. E., Campbell, K. P. (2003). Dystrophin-Glycoprotein Complex: Post-translational Processing and Dystroglycan Function. J. Biol. Chem. 278: 15457-15460 [Full Text]  
• Ebert, J. G., Zelenka, M., Gath, I., Godtel-Armbrust, U., Forstermann, U. (2003). Colocalization but differential regulation of neuronal NO synthase and nicotinic acetylcholine receptor in C2C12 myotubes. Am. J. Physiol. Cell Physiol. 284: C1065-C1072 [Abstract] [Full Text]  
• Thomas, G. D., Shaul, P. W., Yuhanna, I. S., Froehner, S. C., Adams, M. E. (2003). Vasomodulation by Skeletal Muscle-Derived Nitric Oxide Requires {alpha}-Syntrophin-Mediated Sarcolemmal Localization of Neuronal Nitric Oxide Synthase. Circ. Res. 92: 554-560 [Abstract] [Full Text]  
• Bailey, S. J., Stocksley, M. A., Buckel, A., Young, C., Slater, C. R. (2003). Voltage-Gated Sodium Channels and AnkyrinG Occupy a Different Postsynaptic Domain from Acetylcholine Receptors from an Early Stage of Neuromuscular Junction Maturation in Rats. J. Neurosci. 23: 2102-2111 [Abstract] [Full Text]  
• Grady, R. M., Akaaboune, M., Cohen, A. L., Maimone, M. M., Lichtman, J. W., Sanes, J. R. (2003). Tyrosine-phosphorylated and nonphosphorylated isoforms of {alpha}-dystrobrevin: roles in skeletal muscle and its neuromuscular and myotendinous junctions. JCB 160: 741-752 [Abstract] [Full Text]  
• Ou, Y., Strege, P., Miller, S. M., Makielski, J., Ackerman, M., Gibbons, S. J., Farrugia, G. (2003). Syntrophin gamma 2 Regulates SCN5A Gating by a PDZ Domain-mediated Interaction. J. Biol. Chem. 278: 1915-1923 [Abstract] [Full Text]  
• Hosaka, Y., Yokota, T., Miyagoe-Suzuki, Y., Yuasa, K., Imamura, M., Matsuda, R., Ikemoto, T., Kameya, S., Takeda, S.'i. (2002). {alpha}1-Syntrophin-deficient skeletal muscle exhibits hypertrophy and aberrant formation of neuromuscular junctions during regeneration. JCB 158: 1097-1107 [Abstract] [Full Text]  
• Rybakova, I. N., Patel, J. R., Davies, K. E., Yurchenco, P. D., Ervasti, J. M. (2002). Utrophin Binds Laterally along Actin Filaments and Can Couple Costameric Actin with Sarcolemma When Overexpressed in Dystrophin-deficient Muscle. Mol. Biol. Cell 13: 1512-1521 [Abstract] [Full Text]  
• Blake, D. J., Weir, A., Newey, S. E., Davies, K. E. (2002). Function and Genetics of Dystrophin and Dystrophin-Related Proteins in Muscle. Physiol. Rev. 82: 291-329 [Abstract] [Full Text]  
• Neely, J. D., Amiry-Moghaddam, M., Ottersen, O. P., Froehner, S. C., Agre, P., Adams, M. E. (2001). Syntrophin-dependent expression and localization of Aquaporin-4 water channel protein. Proc. Natl. Acad. Sci. USA 98: 14108-14113 [Abstract] [Full Text]  
• Stamler, J. S., Meissner, G. (2001). Physiology of Nitric Oxide in Skeletal Muscle. Physiol. Rev. 81: 209-237 [Abstract] [Full Text]  
• Adams, M. E., Kramarcy, N., Krall, S. P., Rossi, S. G., Rotundo, R. L., Sealock, R., Froehner, S. C. (2000). Absence of {alpha}-Syntrophin Leads to Structurally Aberrant Neuromuscular Synapses Deficient in Utrophin. JCB 150: 1385-1398 [Abstract] [Full Text]  
• Crawford, G. E., Faulkner, J. A., Crosbie, R. H., Campbell, K. P., Froehner, S. C., Chamberlain, J. S. (2000). Assembly of the Dystrophin-associated Protein Complex Does Not Require the Dystrophin COOH-terminal Domain. JCB 150: 1399-1410 [Abstract] [Full Text]  
• Rafael, J. A., Townsend, E. R., Squire, S. E., Potter, A. C., Chamberlain, J. S., Davies, K. E. (2000). Dystrophin and utrophin influence fiber type composition and post-synaptic membrane structure. Hum Mol Genet 9: 1357-1367 [Abstract] [Full Text]  
• Claudepierre, T, Dalloz, C, Mornet, D, Matsumura, K, Sahel, J, Rendon, A (2000). Characterization of the intermolecular associations of the dystrophin-associated glycoprotein complex in retinal Muller glial cells. J. Cell Sci. 113: 3409-3417 [Abstract]  
• Loh, N., Newey, S., Davies, K., Blake, D. (2000). Assembly of multiple dystrobrevin-containing complexes in the kidney. J. Cell Sci. 113: 2715-2724 [Abstract]  
• Durbeej, M., Campbell, K. P. (1999). Biochemical Characterization of the Epithelial Dystroglycan Complex. J. Biol. Chem. 274: 26609-26616 [Abstract] [Full Text]  
• Wilson, J., Putt, W., Jimenez, C., Edwards, Y. H. (1999). Up71 and Up140, two novel transcripts of utrophin that are homologues of short forms of dystrophin. Hum Mol Genet 8: 1271-1278 [Abstract] [Full Text]  
• Hasegawa, M., Cuenda, A., Spillantini, M. G., Thomas, G. M., Buee-Scherrer, V., Cohen, P., Goedert, M. (1999). Stress-activated Protein Kinase-3 Interacts with the PDZ Domain of alpha 1-Syntrophin. A MECHANISM FOR SPECIFIC SUBSTRATE RECOGNITION. J. Biol. Chem. 274: 12626-12631 [Abstract] [Full Text]  
• Hashida-Okumura, A., Okumura, N., Iwamatsu, A., Buijs, R. M., Romijn, H. J., Nagai, K. (1999). Interaction of Neuronal Nitric-oxide Synthase with {alpha}1-Syntrophin in Rat Brain. J. Biol. Chem. 274: 11736-11741 [Abstract] [Full Text]  
• Kachinsky, A. M., Froehner, S. C., Milgram, S. L. (1999). A PDZ-containing Scaffold Related to the Dystrophin Complex at the Basolateral Membrane of Epithelial Cells. JCB 145: 391-402 [Abstract] [Full Text]  
• Kameya, S., Miyagoe, Y., Nonaka, I., Ikemoto, T., Endo, M., Hanaoka, K., Nabeshima, Y.-i., Takeda, S.'i. (1999). alpha 1-Syntrophin Gene Disruption Results in the Absence of Neuronal-type Nitric-oxide Synthase at the Sarcolemma but Does Not Induce Muscle Degeneration. J. Biol. Chem. 274: 2193-2200 [Abstract] [Full Text]  
• Huber, A., Saur, D., Kurjak, M., Schusdziarra, V., Allescher, H.-D. (1998). Characterization and splice variants of neuronal nitric oxide synthase in rat small intestine. Am. J. Physiol. Gastrointest. Liver Physiol. 275: G1146-G1156 [Abstract] [Full Text]  
• Peters, M. F., Sadoulet-Puccio, H. M., Mark Grady, R., Kramarcy, N. R., Kunkel, L. M., Sanes, J. R., Sealock, R., Froehner, S. C. (1998). Differential Membrane Localization and Intermolecular Associations of alpha -Dystrobrevin Isoforms in Skeletal Muscle. JCB 142: 1269-1278 [Abstract] [Full Text]  
• Nawrotzki, R, Loh, N., Ruegg, M., Davies, K., Blake, D. (1998). Characterisation of alpha-dystrobrevin in muscle. J. Cell Sci. 111: 2595-2605 [Abstract]  
• Blake, D. J., Nawrotzki, R., Loh, N. Y., Gorecki, D. C., Davies, K. E. (1998). beta -dystrobrevin, a member of the dystrophin-related protein family. Proc. Natl. Acad. Sci. USA 95: 241-246 [Abstract] [Full Text]  
• Gee, S. H., Madhavan, R., Levinson, S. R., Caldwell, J. H., Sealock, R., Froehner, S. C. (1998). Interaction of Muscle and Brain Sodium Channels with Multiple Members of the Syntrophin Family of Dystrophin-Associated Proteins. J. Neurosci. 18: 128-137 [Abstract] [Full Text]  
• Peters, M. F., O'Brien, K. F., Sadoulet-Puccio, H. M., Kunkel, L. M., Adams, M. E., Froehner, S. C. (1997). beta -Dystrobrevin, a New Member of the Dystrophin Family. IDENTIFICATION, CLONING, AND PROTEIN ASSOCIATIONS. J. Biol. Chem. 272: 31561-31569 [Abstract] [Full Text]  
• Sadoulet-Puccio, H. M., Rajala, M., Kunkel, L. M. (1997). Dystrobrevin and dystrophin: An interaction through coiled-coil motifs. Proc. Natl. Acad. Sci. USA 94: 12413-12418 [Abstract] [Full Text]  
• Piluso, G., Mirabella, M., Ricci, E., Belsito, A., Abbondanza, C., Servidei, S., Puca, A. A., Tonali, P., Puca, G. A., Nigro, V. (2000). gamma 1- and gamma 2-Syntrophins, Two Novel Dystrophin-binding Proteins Localized in Neuronal Cells. J. Biol. Chem. 275: 15851-15860 [Abstract] [Full Text]  
• Peters, M. F., Ross, C. A. (2001). Isolation of a 40-kDa Huntingtin-associated Protein. J. Biol. Chem. 276: 3188-3194 [Abstract] [Full Text]  
• McDearmon, E. L., Combs, A. C., Ervasti, J. M. (2001). Differential Vicia villosa Agglutinin Reactivity Identifies Three Distinct Dystroglycan Complexes in Skeletal Muscle. J. Biol. Chem. 276: 35078-35086 [Abstract] [Full Text]  
• Hogan, A., Shepherd, L., Chabot, J., Quenneville, S., Prescott, S. M., Topham, M. K., Gee, S. H. (2001). Interaction of gamma 1-Syntrophin with Diacylglycerol Kinase-zeta . REGULATION OF NUCLEAR LOCALIZATION BY PDZ INTERACTIONS. J. Biol. Chem. 276: 26526-26533 [Abstract] [Full Text]  
• Adams, M. E., Mueller, H. A., Froehner, S. C. (2001). In vivo requirement of the {alpha}-syntrophin PDZ domain for the sarcolemmal localization of nNOS and aquaporin-4. JCB 155: 113-122 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents