Abstract
Syntrophin is known to be a component of the dystrophin-glycoprotein complex (DGC), a membrane/cytoskeleton-anchoring structure that is essential for the maintenance of viability of sarcolemma. We purified DGC from hearts of human and several animal species, and compared their protein composition. While almost all components of DGC were present in various species, proteins with the apparent molecular mass of 50–65 kDa corresponding to syntrophin isoforms were very different among them. Three isoforms of syntrophin (α1, β1, β2) were expressed in hamster, rat and canine ventricles, whereas only α1-isoform was mainly expressed in human and rabbit ventricles. Immunohistochemical analysis revealed that α1-and β2-syntrophins were co-localized in sarcolemma and in T-tubules of canine ventricles. However, despite membrane localization of most syntrophins, subcellular fractionation revealed that part of syntrophins were recovered in the cytosolic fraction devoid of other components of DGC, raising the possibility that syntrophins may play multiple roles in various intracellular sites of cardiac muscle cells. Species-dependent expression and unique subcellular localization of syntrophins in cardiac muscle may contribute to the variable severity of muscle dysgenesis caused by the same primary defect in components of DGC of human and other animal species. (Mol Cell Biochem 268: 59–66, 2005)
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Abbreviations
- DGC:
-
dystrophin–glycoprotein complex
- DAP:
-
dystrophin-associated protein
- SG:
-
sarcoglycan
- DG:
-
dystroglycan
- WGA:
-
wheat germ agglutinin
- NAG:
-
N-acetyl glucosamine
- CBB:
-
Coomassie brilliant blue
- DTT:
-
dithiothreitol
- PMSF:
-
phenylmethylsulfonyl fluoride
- MBP:
-
maltose binding protein
- GST:
-
glutathione S-transferase
- SDS-PAGE:
-
sodium dodecyl sulfate-polyacrylamide gel electrophoresis
References
Hunsaker RH, Fulkerson PK, Barry FJ, Lewis RP, Leier CV, Unverferth DV: Cardiac function in Duchenne’s muscular dystrophy Results of 10-year follow-up study and noninvasive tests. Am J Med 73: 235–238, 1982
Torres LF, Duchen LW: The mutant mdx: Inherited myopathy in the mouse. Morphological studies of nerves, muscles and end-plates. Brain 110: 269–299, 1987
Towbin JA, Hejtmancik JF, Brink P, Gelb B, Zhu XM, Chamberlain JS, McCabe ERB, Swift M: X-linked dilated cardiomyopathy molecular genetic evidence of linkage to the Duchenne muscular dystrophy (dystrophin) gene at the Xp21 locus. Circulation 87: 1854–1865, 1993
Piccolo F, Roberds SL, Jeanpierre M, Leturcq F, Azibi K, Beldjord C, Carrié A, Récan D, Chaouch M, Reghis A, El Kerch F, Sefiani A, Voit T, Merlini L, Collin H, Eymard B, Beckmann JS, Romero NB, Tomé FMS, Fardeau M, Campbell KP, Kaplan J-C: Primary adhalinopathy: A common cause of autosomal recessive muscular dystrophy of variable severity. Nature Genetics 10: 243–245, 1995
Roberds SL, Ervasti JM, Anderson RD, Ohlendieck K, Kahl SD, Zoloto D, Campbell KP: Disruption of the dystrophin-glycoprotein complex in the cardiomyopathic hamster. J Biol Chem 268: 11496–11499, 1993
Ahn AH, Kunkel LM: The structural and functional diversity of dystrophin. Nature Genetics 3: 283–291, 1993
Klietsch R, Ervasti JM, Arnold W, Campbell KP, Jorgensen AO: Dystrophin-glycoprotein complex and laminin colocalize to the sarcolemma and transverse tubules of cardiac muscle. Circ Res 72: 349–360, 1993
Frank JS, Mottino G, Chen F, Peri V, Holland P, Tuana BS: Subcellular distribution of dystrophin in isolated adult and neonatal cardiac myocytes. Am J Physiol 267: C1707–C1716, 1994
Meng H, Leddy JJ, Frank J, Holland P, Tuana BS: The association of cardiac dystrophin with myofibrils/Z-disc regions in cardiac muscle suggests a novel role in the contractile apparatus. J Biol Chem 271:12364–12371, 1996
Rivier F, Robert A, Hugon G, Bonet-Kerrache A, Nigro V, Fehrentz JA, Martinez J, Mornet D: Dystrophin and utrophin complexed with different associated proteins in cardiac Purkinje fibers. Histochem J 31: 425–432, 1999
Ahn AH, Freener CA, Gussoni E, Yoshida M, Ozawa E, Kunkel LM: The three human syntrophin genes are expressed in diverse tissues have distinct chromosomal locations and each bind to dystrophin and its relatives. J Biol Chem 271: 2724–2730, 1996
Piluso G, Mirabella M, Ricci E, Belsito A, Abbondanza C, Servidei S, Puca AA, Tonali P, Puca GA, Nigro V: γ1- and γ2-Syntrophins, two novel dystrophin-binding proteins localized in neuronal cells. J Biol Chem 275: 15851–15860, 2000
Iwata Y, Pan Y, Hanada H, Yoshida T, Shigekawa M: Dystrophin-dystrophin associated protein complex purified from hamster cardiac muscle. Comparison of the complexes from cardiac and skeletal muscles of hamster and rabbit. J Mol Cell Cardiol 28: 2501–2509, 1996
Tawada-Iwata Y, Imagawa T, Yoshida A, Takahashi M, Nakamura H, Shigekawa M: Increased mechanical extraction of T-tubule/junctional SR from cardiomyopathic hamster heart. Am J Physiol 264: H1447–H1453, 1993
Matthew P, Adams ME, Froehner SC: Differential association of syntrophin pairs with the dystrophin complex. J Cell Biol 138: 81–93, 1997
Sampaolesi M, Yoshida Y, Iwata Y, Hanada H, Shigekawa M: Stretch-induced cell damage in sarcoglycan-deficient myotubes. Pflugers Arch 442: 161–170, 2001
Froehner SC, Murnane AA, Tobler M, Peng HB, Sealock R: A postsynaptic Mr 58000 (58k) protein concentrate at acetylcholine receptor-rich sites in Torpedo electroplaques and skeletal muscle. J Cell Biol 104: 1633–1646, 1987
Iwata Y, Nakamura H, Mizuno Y, Yoshida M, Ozawa E, Shigekawa, M: Defective association of dystrophin with sarcolemmal glycoproteins in the cardiomyopathic hamster heart. FEBS Lett 329: 227–231, 1993
Peters MF, Adams ME, Froehner SC: Differential association of syntrophin pairs with the dystrophin complex. J Cell Biol 138: 81–93, 1997
Matthew FP, Kramarcy NR, Sealock R, Froehner SC: β2-Syntrophin: Localization at the neuromuscular junction in skeletal muscle. Neuro Report 5: 1577–1580, 1994
Iwata Y, Pan Y, Yoshida T, Hanada H, Shigekawa M: α1-Syntrophin has distinct binding sites for actin and calmodulin. FEBS Lett 423: 173–177, 1998
Newbell BJ, Anderson JT, Jarrett HW: Ca2+-calmodulin binding to mouse alphal syntrophin: Syntrophin is also a Ca2+-binding protein. Biochemistry 36: 1295–305, 1997
Chockalingam PS, Gee SH, Jarrett HW: Pleckstrin homology domain 1 of mouse α1-syntrophin binds phosphatidylinositol 4,5-biphosphate. Biochemistry 38: 5596–5602, 1999
Dwyer TM, Froehner SC: Direct binding of Torpedo syntrophin to dystrophin and the 87 kDa dystrophin homologue. FEES Lett 375: 91–94, 1995
Brenman JE, Chao DS, Gee SH, McGee AW, Craven SE, Santillano DR, Wu Z: Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alphal-syntrophin mediated by PDZ domains. Cell 84: 757–767, 1996
Gee SH, Madhavan R, Levinson SR, Caldwell JH, Sealock R, Froehner SC: Interaction of muscle and brain sodium channels with multiple members of the syntrophin family of dystrophin-associated proteins. J Neurosci 274: 128–137, 1998
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Iwata, Y., Shigekawa, M. & Wakabayashi, S. Cardiac syntrophin isoforms: Species-dependent expression, association with dystrophin complex and subcellular localization. Mol Cell Biochem 268, 59–66 (2005). https://doi.org/10.1007/s11010-005-2998-z
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DOI: https://doi.org/10.1007/s11010-005-2998-z