The Journal of Membrane Biology

, Volume 251, Issue 4, pp 535–550 | Cite as

Biochemical and Functional Interplay Between Ion Channels and the Components of the Dystrophin-Associated Glycoprotein Complex

  • Margarita Leyva-Leyva
  • Alejandro Sandoval
  • Ricardo FelixEmail author
  • Ricardo González-RamírezEmail author
Topical Review


Dystrophin is a cytoskeleton-linked membrane protein that binds to a larger multiprotein assembly called the dystrophin-associated glycoprotein complex (DGC). The deficiency of dystrophin or the components of the DGC results in the loss of connection between the cytoskeleton and the extracellular matrix with significant pathophysiological implications in skeletal and cardiac muscle as well as in the nervous system. Although the DGC plays an important role in maintaining membrane stability, it can also be considered as a versatile and flexible molecular complex that contribute to the cellular organization and dynamics of a variety of proteins at specific locations in the plasma membrane. This review deals with the role of the DGC in transmembrane signaling by forming supramolecular assemblies for regulating ion channel localization and activity. These interactions are relevant for cell homeostasis, and its alterations may play a significant role in the etiology and pathogenesis of various disorders affecting muscle and nerve function.


DGC Dystrophin Ion channels NaV channels CaV channels TRP 



This work was partially supported by funds from The National Council for Science and Technology (Conacyt, Mexico; Grant No. 221660) to R.F.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

232_2018_36_MOESM1_ESM.jpg (135 kb)
Suppl Fig 1. Molecular organization of voltage-gated Ca2+ (CaV), Na+ (NaV) and inward rectifying K+ (Kir) channels. The pore-forming α-subunit of NaV channels contains four domains each with six transmembrane segments with the N- and C-termini located in the cytoplasm. Ancillary β-subunits are single transmembrane proteins that co-assembles with the NaV α-subunit. CaV channels show a similar topology to NaV channels in their α-subunits but can be associated with different auxiliary subunits named α2δ, β and occasionally a γ-subunit with four transmembrane segments. BK channels comprise four ion-conducting α-subunits and in some tissues β auxiliary subunits. The α-subunits alone are sufficient to form a functional channel. These channels have an extra transmembrane domain that places its amino-terminal outside the cell. It also has a large intracellular carboxyl-terminus region that confers Ca2+ sensitivity to the channel complex. Kir channels contain two transmembrane (2 TM) and one pore-forming domain. The 2 TM domains assemble into a tetrameric ion-conducting Kir channel. Last, the membrane topology of cation channels of the transient receptor potential canonical (TRPC) family consists of six transmembrane spanning segments that are linked by short extracellular or intracellular loops (JPG 136 KB)
232_2018_36_MOESM2_ESM.jpg (54 kb)
Suppl Fig 2. Molecular organization of voltage-gated Ca2+ (CaV), Na+ (NaV) and inward rectifying K+ (Kir) channels. The pore-forming α-subunit of NaV channels contains four domains each with six transmembrane segments with the N- and C-termini located in the cytoplasm. Ancillary β-subunits are single transmembrane proteins that co-assembles with the NaV α-subunit. CaV channels show a similar topology to NaV channels in their α-subunits but can be associated with different auxiliary subunits named α2δ, β and occasionally a γ-subunit with four transmembrane segments. BK channels comprise four ion-conducting α-subunits and in some tissues β auxiliary subunits. The α-subunits alone are sufficient to form a functional channel. These channels have an extra transmembrane domain that places its amino-terminal outside the cell. It also has a large intracellular carboxyl-terminus region that confers Ca2+ sensitivity to the channel complex. Kir channels contain two transmembrane (2 TM) and one pore-forming domain. The 2 TM domains assemble into a tetrameric ion-conducting Kir channel. Last, the membrane topology of cation channels of the transient receptor potential canonical (TRPC) family consists of six transmembrane spanning segments that are linked by short extracellular or intracellular loops (JPG 54 KB)


  1. Abraham LS, Oh HJ, Sancar F, Richmond JE, Kim H (2010). An alpha-catulin homologue controls neuromuscular function through localization of the dystrophin complex and BK channels in Caenorhabditis elegans. PLoS Genet 6:e1001077PubMedPubMedCentralCrossRefGoogle Scholar
  2. Adams ME, Anderson KN, Froehner SC (2010) The alpha-syntrophin PH and PDZ domains scaffold acetylcholine receptors, utrophin, and neuronal nitric oxide synthase at the neuromuscular junction. J Neurosci 30:11004–11010PubMedPubMedCentralCrossRefGoogle Scholar
  3. Adams ME, Butler MH, Dwyer TM, Peters MF, Murnane AA, Froehner SC (1993). Two forms of mouse syntrophin, a 58 kd dystrophin-associated protein, differ in primary structure and tissue distribution. Neuron 11:531–540CrossRefGoogle Scholar
  4. Allen DG (2004) Skeletal muscle function: role of ionic changes in fatigue, damage and disease. Clin Exp Pharmacol Physiol 31:485–493PubMedCrossRefGoogle Scholar
  5. Allikian MJ, McNally EM (2007) Processing and assembly of the dystrophin glycoprotein complex. Traffic 8:177–183PubMedCrossRefGoogle Scholar
  6. Amberg GC, Bonev AD, Rossow CF, Nelson MT, Santana LF (2003) Modulation of the molecular composition of large conductance, Ca(2+) activated K(+) channels in vascular smooth muscle during hypertension. J Clin Invest 112:717–724PubMedPubMedCentralCrossRefGoogle Scholar
  7. Amiry-Moghaddam M, Otsuka T, Hurn PD, Traystman RJ, Haug FM, Froehner SC, Adams ME, Neely JD, Agre P, Ottersen OP, Bhardwaj A (2003) An alpha-syntrophin-dependent pool of AQP4 in astroglial end-feet confers bidirectional water flow between blood and brain. Proc Natl Acad Sci USA 100:2106–2111PubMedCrossRefGoogle Scholar
  8. Bardoni A, Felisari G, Sironi M, Comi G, Lai M, Robotti M, Bresolin N (2000) Loss of Dp140 regulatory sequences is associated with cognitive impairment in dystrophinopathies. Neuromuscul Disord 10:194–199PubMedCrossRefGoogle Scholar
  9. Batchelor CL, Winder SJ (2006) Sparks, signals and shock absorbers: how dystrophin loss causes muscular dystrophy. Trends Cell Biol 16:198–205PubMedCrossRefGoogle Scholar
  10. Bhat HF, Adams ME, Khanday FA (2013) Syntrophin proteins as Santa Claus: role(s) in cell signal transduction. Cell Mol Life Sci 70:2533–2554PubMedCrossRefGoogle Scholar
  11. Bhat HF, Mir SS, Dar KB, Bhat ZF, Shah RA, Ganai NA (2017). ABC of multifaceted dystrophin glycoprotein complex (DGC). J Cell Physiol 233(7):5142–5159Google Scholar
  12. Billard C, Gillet P, Barthez M, Hommet C, Bertrand P (1998) Reading ability and processing in Duchenne muscular dystrophy and spinal muscular atrophy. Dev Med Child Neurol 40:12–20PubMedCrossRefGoogle Scholar
  13. Blake DJ, Weir A, Newey SE, Davies KE (2002) Function and genetics of dystrophin and dystrophin-related proteins in muscle. Physiol Rev 82:291–329PubMedCrossRefGoogle Scholar
  14. Bloch RJ, Capetanaki Y, O’Neill A, Reed P, Williams MW, Resneck WG, Porter NC, Ursitti JA (2002). Costameres: repeating structures at the sarcolemma of skeletal muscle. Clin Orthop Relat Res 403:S203–S210CrossRefGoogle Scholar
  15. Bovolenta M, Erriquez D, Valli E, Brioschi S, Scotton C, Neri M, Falzarano MS, Gherardi S, Fabris M, Rimessi P, Gualandi F, Perini G, Ferlini A (2012) The DMD locus harbours multiple long non-coding RNAs which orchestrate and control transcription of muscle dystrophin mRNA isoforms. PLoS ONE 7:e45328PubMedPubMedCentralCrossRefGoogle Scholar
  16. Bowe MA, Mendis DB, Fallon JR (2000) The small leucine-rich repeat proteoglycan biglycan binds to alpha-dystroglycan and is upregulated in dystrophic muscle. J Cell Biol 148:801–810PubMedPubMedCentralCrossRefGoogle Scholar
  17. Bringmann A, Pannicke T, Grosche J, Francke M, Wiedemann P, Skatchkov SN, Osborne NN, Reichenbach A (2006) Muller cells in the healthy and diseased retina. Prog Retin Eye Res 25:397–424PubMedCrossRefGoogle Scholar
  18. Broderick MJ, Winder SJ (2005) Spectrin, alpha-actinin, and dystrophin. Adv Protein Chem 70:203–246PubMedCrossRefGoogle Scholar
  19. Butler MH, Douville K, Murnane AA, Kramarcy NR, Cohen JB, Sealock R, Froehner SC (1992) Association of the Mr 58,000 postsynaptic protein of electric tissue with Torpedo dystrophin and the Mr 87,000 postsynaptic protein. J Biol Chem 267:6213–6218PubMedGoogle Scholar
  20. Campbell KP (1995) Three muscular dystrophies: loss of cytoskeleton-extracellular matrix linkage. Cell 80:675–679PubMedCrossRefGoogle Scholar
  21. Campbell KP, Kahl SD (1989) Association of dystrophin and an integral membrane glycoprotein. Nature 338:259–262PubMedCrossRefGoogle Scholar
  22. Carlson CG (1998) The dystrophinopathies: an alternative to the structural hypothesis. Neurobiol Dis 5:3–15PubMedCrossRefGoogle Scholar
  23. Carre-Pierrat M, Grisoni K, Gieseler K, Mariol MC, Martin E, Jospin M, Allard B, Segalat L (2006) The SLO-1 BK channel of Caenorhabditis elegans is critical for muscle function and is involved in dystrophin-dependent muscle dystrophy. J Mol Biol 358:387–395PubMedCrossRefGoogle Scholar
  24. Catterall WA (2011) Voltage-gated calcium channels. Cold Spring Harb Perspect Biol 3:a003947PubMedPubMedCentralCrossRefGoogle Scholar
  25. Catterall WA (2012) Voltage-gated sodium channels at 60: structure, function and pathophysiology. J Physiol 590:2577–2589PubMedPubMedCentralCrossRefGoogle Scholar
  26. Catterall WA, Goldin AL, Waxman SG (2005) International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels. Pharmacol Rev 57:397–409PubMedCrossRefGoogle Scholar
  27. Chen YJ, Spence HJ, Cameron JM, Jess T, Ilsley JL, Winder SJ (2003). Direct interaction of beta-dystroglycan with F-actin. Biochem J 375:329–337CrossRefGoogle Scholar
  28. Cohn RD, Durbeej M, Moore SA, Coral-Vazquez R, Prouty S, Campbell KP (2001) Prevention of cardiomyopathy in mouse models lacking the smooth muscle sarcoglycan-sarcospan complex. J Clin Invest 107:R1–R7CrossRefGoogle Scholar
  29. Compton AG, Cooper ST, Hill PM, Yang N, Froehner SC, North KN (2005) The syntrophin-dystrobrevin subcomplex in human neuromuscular disorders. J Neuropathol Exp Neurol 64:350–361PubMedCrossRefGoogle Scholar
  30. Connors NC, Adams ME, Froehner SC, Kofuji P (2004) The potassium channel Kir4.1 associates with the dystrophin-glycoprotein complex via alpha-syntrophin in glia. J Biol Chem 279:28387–28392PubMedCrossRefGoogle Scholar
  31. Connors NC, Kofuji P (2002) Dystrophin Dp71 is critical for the clustered localization of potassium channels in retinal glial cells. J Neurosci 22:4321–4327PubMedCrossRefGoogle Scholar
  32. Constantin B (2014) Dystrophin complex functions as a scaffold for signalling proteins. Biochim Biophys Acta 1838:635–642PubMedCrossRefGoogle Scholar
  33. Coral-Vazquez R, Cohn RD, Moore SA, Hill JA, Weiss RM, Davisson RL, Straub V, Barresi R, Bansal D, Hrstka RF, Williamson R, Campbell KP (1999). Disruption of the sarcoglycan-sarcospan complex in vascular smooth muscle: a novel mechanism for cardiomyopathy and muscular dystrophy. Cell 98:465–474CrossRefGoogle Scholar
  34. Crosbie RH, Heighway J, Venzke DP, Lee JC, Campbell KP (1997) Sarcospan, the 25-kDa transmembrane component of the dystrophin-glycoprotein complex. J Biol Chem 272:31221–31224PubMedCrossRefGoogle Scholar
  35. Crosbie RH, Lebakken CS, Holt KH, Venzke DP, Straub V, Lee JC, Grady RM, Chamberlain JS, Sanes JR, Campbell KP (1999) Membrane targeting and stabilization of sarcospan is mediated by the sarcoglycan subcomplex. J Cell Biol 145:153–165PubMedPubMedCentralCrossRefGoogle Scholar
  36. Dalloz C, Sarig R, Fort P, Yaffe D, Bordais A, Pannicke T, Grosche J, Mornet D, Reichenbach A, Sahel J, Nudel U, Rendon A (2003) Targeted inactivation of dystrophin gene product Dp71: phenotypic impact in mouse retina. Hum Mol Genet 12:1543–1554PubMedCrossRefGoogle Scholar
  37. Davies AG, Pierce-Shimomura JT, Kim H, VanHoven MK, Thiele TR, Bonci A, Bargmann CI, McIntire SL (2003). A central role of the BK potassium channel in behavioral responses to ethanol in C. elegans. Cell 115:655–666CrossRefGoogle Scholar
  38. Deconinck AE, Rafael JA, Skinner JA, Brown SC, Potter AC, Metzinger L, Watt DJ, Dickson JG, Tinsley JM, Davies KE (1997). Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy. Cell 90:717–727CrossRefGoogle Scholar
  39. Deval E, Levitsky DO, Marchand E, Cantereau A, Raymond G, Cognard C (2002). Na(+)/Ca(2+) exchange in human myotubes: intracellular calcium rises in response to external sodium depletion are enhanced in DMD. Neuromuscul Disord 12:665–673CrossRefGoogle Scholar
  40. Djukic B, Casper KB, Philpot BD, Chin LS, McCarthy KD (2007) Conditional knock-out of Kir4.1 leads to glial membrane depolarization, inhibition of potassium and glutamate uptake, and enhanced short-term synaptic potentiation. J Neurosci 27:11354–11365PubMedCrossRefGoogle Scholar
  41. Dolphin AC (2012) Calcium channel auxiliary alpha2delta and beta subunits: trafficking and one step beyond. Nat Rev Neurosci 13:542–555PubMedCrossRefGoogle Scholar
  42. Dolphin AC (2016) Voltage-gated calcium channels and their auxiliary subunits: physiology and pathophysiology and pharmacology. J Physiol 594:5369–5390PubMedPubMedCentralCrossRefGoogle Scholar
  43. Doyle DA, Lee A, Lewis J, Kim E, Sheng M, MacKinnon R (1996) Crystal structures of a complexed and peptide-free membrane protein-binding domain: molecular basis of peptide recognition by PDZ. Cell 85:1067–1076PubMedCrossRefGoogle Scholar
  44. Dunn JF, Bannister N, Kemp GJ, Publicover SJ (1993) Sodium is elevated in mdx muscles: ionic interactions in dystrophic cells. J Neurol Sci 114:76–80PubMedCrossRefGoogle Scholar
  45. Ervasti JM, Campbell KP (1991) Membrane organization of the dystrophin-glycoprotein complex. Cell 66:1121–1131PubMedCrossRefGoogle Scholar
  46. Ervasti JM, Ohlendieck K, Kahl SD, Gaver MG, Campbell KP (1990) Deficiency of a glycoprotein component of the dystrophin complex in dystrophic muscle. Nature 345:315–319PubMedCrossRefGoogle Scholar
  47. Ettinger AJ, Feng G, Sanes JR (1997) epsilon-Sarcoglycan, a broadly expressed homologue of the gene mutated in limb-girdle muscular dystrophy 2D. J Biol Chem 272:32534–32538PubMedCrossRefGoogle Scholar
  48. Felisari G, Martinelli Boneschi F, Bardoni A, Sironi M, Comi GP, Robotti M, Turconi AC, Lai M, Corrao G, Bresolin N (2000) Loss of Dp140 dystrophin isoform and intellectual impairment in Duchenne dystrophy. Neurology 55:559–564PubMedCrossRefGoogle Scholar
  49. Felix R (1999) Voltage-dependent Ca2+ channel alpha2delta auxiliary subunit: structure, function and regulation. Recept Channels 6:351–362PubMedGoogle Scholar
  50. Felix R (2005) Molecular regulation of voltage-gated Ca2+ channels. J Recept Signal Transduct Res 25:57–71PubMedCrossRefGoogle Scholar
  51. Felix R, Calderon-Rivera A, Andrade A (2013) Regulation of high-voltage-activated Ca channel function, trafficking, and membrane stability by auxiliary subunits. Wiley Interdiscip Rev Membr Transp Signal 2:207–220PubMedPubMedCentralCrossRefGoogle Scholar
  52. Finsterer J (2006) Cardiopulmonary support in duchenne muscular dystrophy. Lung 184:205–215PubMedCrossRefGoogle Scholar
  53. Formigli L, Sassoli C, Squecco R, Bini F, Martinesi M, Chellini F, Luciani G, Sbrana F, Zecchi-Orlandini S, Francini F, Meacci E (2009) Regulation of transient receptor potential canonical channel 1 (TRPC1) by sphingosine 1-phosphate in C2C12 myoblasts and its relevance for a role of mechanotransduction in skeletal muscle differentiation. J Cell Sci 122:1322–1333PubMedCrossRefGoogle Scholar
  54. Franco A Jr, Lansman JB (1990) Calcium entry through stretch-inactivated ion channels in mdx myotubes. Nature 344:670–673PubMedCrossRefGoogle Scholar
  55. Friedrich O, Both M, Gillis JM, Chamberlain JS, Fink RH (2004). Mini-dystrophin restores L-type calcium currents in skeletal muscle of transgenic mdx mice. J Physiol 555:251–265CrossRefGoogle Scholar
  56. Friedrich O, von Wegner F, Chamberlain JS, Fink RH, Rohrbach P (2008) L-type Ca2+ channel function is linked to dystrophin expression in mammalian muscle. PLoS ONE 3:e1762PubMedPubMedCentralCrossRefGoogle Scholar
  57. Gandini MA, Felix R (2015) Molecular and functional interplay of voltage-gated Ca(2)(+) channels with the cytoskeleton. Curr Mol Pharmacol 8:69–80PubMedCrossRefGoogle Scholar
  58. Gardiol D (2012) PDZ-containing proteins as targets in human pathologies. FEBS J 279:3529PubMedCrossRefGoogle Scholar
  59. Gavillet B, Rougier JS, Domenighetti AA, Behar R, Boixel C, Ruchat P, Lehr HA, Pedrazzini T, Abriel H (2006) Cardiac sodium channel Nav1.5 is regulated by a multiprotein complex composed of syntrophins and dystrophin. Circ Res 99:407–414PubMedCrossRefGoogle Scholar
  60. Gee SH, Madhavan R, Levinson SR, Caldwell JH, Sealock R, Froehner SC (1998). Interaction of muscle and brain sodium channels with multiple members of the syntrophin family of dystrophin-associated proteins. J Neurosci 18:128–137CrossRefGoogle Scholar
  61. Gieseler K, Bessou C, Segalat L (1999) Dystrobrevin- and dystrophin-like mutants display similar phenotypes in the nematode Caenorhabditis elegans. Neurogenetics 2:87–90PubMedCrossRefGoogle Scholar
  62. Godfrey C, Foley AR, Clement E, Muntoni F (2011) Dystroglycanopathies: coming into focus. Curr Opin Genet Dev 21:278–285PubMedCrossRefGoogle Scholar
  63. Gottlieb P, Folgering J, Maroto R, Raso A, Wood TG, Kurosky A, Bowman C, Bichet D, Patel A, Sachs F, Martinac B, Hamill OP, Honore E (2008). Revisiting TRPC1 and TRPC6 mechanosensitivity. Pflug Arch 455:1097–1103CrossRefGoogle Scholar
  64. Grady RM, Teng H, Nichol MC, Cunningham JC, Wilkinson RS, Sanes JR (1997). Skeletal and cardiac myopathies in mice lacking utrophin and dystrophin: a model for Duchenne muscular dystrophy. Cell 90:729–738CrossRefGoogle Scholar
  65. Greener MJ, Roberts RG (2000) Conservation of components of the dystrophin complex in Drosophila. FEBS Lett 482:13–18PubMedCrossRefGoogle Scholar
  66. Grewal PK, Holzfeind PJ, Bittner RE, Hewitt JE (2001) Mutant glycosyltransferase and altered glycosylation of alpha-dystroglycan in the myodystrophy mouse. Nat Genet 28:151–154PubMedCrossRefGoogle Scholar
  67. Grisoni K, Martin E, Gieseler K, Mariol MC, Segalat L (2002) Genetic evidence for a dystrophin-glycoprotein complex (DGC) in Caenorhabditis elegans. Gene 294:77–86PubMedCrossRefGoogle Scholar
  68. Guadagno E, Moukhles H (2004) Laminin-induced aggregation of the inwardly rectifying potassium channel, Kir4.1, and the water-permeable channel, AQP4, via a dystroglycan-containing complex in astrocytes. Glia 47:138–149PubMedCrossRefGoogle Scholar
  69. Halayko AJ, Stelmack GL (2005) The association of caveolae, actin, and the dystrophin-glycoprotein complex: a role in smooth muscle phenotype and function? Can J Physiol Pharmacol 83:877–891PubMedCrossRefGoogle Scholar
  70. Hall DD, Dai S, Tseng PY, Malik Z, Nguyen M, Matt L, Schnizler K, Shephard A, Mohapatra DP, Tsuruta F, Dolmetsch RE, Christel CJ, Lee A, Burette A, Weinberg RJ, Hell JW (2013). Competition between alpha-actinin and Ca2+-calmodulin controls surface retention of the L-type Ca2+ channel CaV1.2. Neuron 78:483–497CrossRefGoogle Scholar
  71. Hendriksen JG, Vles JS (2008) Neuropsychiatric disorders in males with duchenne muscular dystrophy: frequency rate of attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder, and obsessive–compulsive disorder. J Child Neurol 23:477–481PubMedCrossRefGoogle Scholar
  72. Hibino H, Fujita A, Iwai K, Yamada M, Kurachi Y (2004) Differential assembly of inwardly rectifying K + channel subunits, Kir4.1 and Kir5.1, in brain astrocytes. J Biol Chem 279:44065–44073PubMedCrossRefGoogle Scholar
  73. Hibino H, Inanobe A, Furutani K, Murakami S, Findlay I, Kurachi Y (2010) Inwardly rectifying potassium channels: their structure, function, and physiological roles. Physiol Rev 90:291–366PubMedCrossRefGoogle Scholar
  74. Hirn C, Shapovalov G, Petermann O, Roulet E, Ruegg UT (2008) Nav1.4 deregulation in dystrophic skeletal muscle leads to Na+ overload and enhanced cell death. J Gen Physiol 132:199–208PubMedPubMedCentralCrossRefGoogle Scholar
  75. Hnia K, Zouiten D, Cantel S, Chazalette D, Hugon G, Fehrentz JA, Masmoudi A, Diment A, Bramham J, Mornet D, Winder SJ (2007). ZZ domain of dystrophin and utrophin: topology and mapping of a beta-dystroglycan interaction site. Biochem J 401:667–677CrossRefGoogle Scholar
  76. Hoffman EP, Brown RH Jr, Kunkel LM (1987) Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 51:919–928PubMedCrossRefGoogle Scholar
  77. Holland PW, Garcia-Fernandez J, Williams NA, Sidow A (1994). Gene duplications and the origins of vertebrate development. Dev Suppl 1994:125–133Google Scholar
  78. Holt KH, Crosbie RH, Venzke DP, Campbell KP (2000) Biosynthesis of dystroglycan: processing of a precursor propeptide. FEBS Lett 468:79–83PubMedCrossRefGoogle Scholar
  79. Ibraghimov-Beskrovnaya O, Ervasti JM, Leveille CJ, Slaughter CA, Sernett SW, Campbell KP (1992) Primary structure of dystrophin-associated glycoproteins linking dystrophin to the extracellular matrix. Nature 355:696–702PubMedCrossRefGoogle Scholar
  80. Ivarsson Y (2012) Plasticity of PDZ domains in ligand recognition and signaling. FEBS Lett 586:2638–2647PubMedCrossRefGoogle Scholar
  81. Iwata Y, Katanosaka Y, Arai Y, Komamura K, Miyatake K, Shigekawa M (2003) A novel mechanism of myocyte degeneration involving the Ca2+-permeable growth factor-regulated channel. J Cell Biol 161:957–967PubMedPubMedCentralCrossRefGoogle Scholar
  82. Iwata Y, Katanosaka Y, Arai Y, Shigekawa M, Wakabayashi S (2009) Dominant-negative inhibition of Ca2+ influx via TRPV2 ameliorates muscular dystrophy in animal models. Hum Mol Genet 18:824–834PubMedCrossRefGoogle Scholar
  83. Jin H, Tan S, Hermanowski J, Bohm S, Pacheco S, McCauley JM, Greener MJ, Hinits Y, Hughes SM, Sharpe PT, Roberts RG (2007) The dystrotelin, dystrophin and dystrobrevin superfamily: new paralogues and old isoforms. BMC Genom 8:19CrossRefGoogle Scholar
  84. Johnson BD, Scheuer T, Catterall WA (2005) Convergent regulation of skeletal muscle Ca2+ channels by dystrophin, the actin cytoskeleton, and cAMP-dependent protein kinase. Proc Natl Acad Sci USA 102:4191–4196PubMedCrossRefGoogle Scholar
  85. Kachinsky AM, Froehner SC, Milgram SL (1999) A PDZ-containing scaffold related to the dystrophin complex at the basolateral membrane of epithelial cells. J Cell Biol 145:391–402PubMedPubMedCentralCrossRefGoogle Scholar
  86. Kim H, Pierce-Shimomura JT, Oh HJ, Johnson BE, Goodman MB, McIntire SL (2009) The dystrophin complex controls bk channel localization and muscle activity in Caenorhabditis elegans. PLoS Genet 5:e1000780PubMedPubMedCentralCrossRefGoogle Scholar
  87. Koenig M, Kunkel LM (1990) Detailed analysis of the repeat domain of dystrophin reveals four potential hinge segments that may confer flexibility. J Biol Chem 265:4560–4566PubMedGoogle Scholar
  88. Koenig M, Monaco AP, Kunkel LM (1988) The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell 53:219–228PubMedCrossRefGoogle Scholar
  89. Koenig X, Rubi L, Obermair GJ, Cervenka R, Dang XB, Lukacs P, Kummer S, Bittner RE, Kubista H, Todt H, Hilber K (2014) Enhanced currents through L-type calcium channels in cardiomyocytes disturb the electrophysiology of the dystrophic heart. Am J Physiol Heart Circ Physiol 306:H564–H573CrossRefGoogle Scholar
  90. Kofuji P, Biedermann B, Siddharthan V, Raap M, Iandiev I, Milenkovic I, Thomzig A, Veh RW, Bringmann A, Reichenbach A (2002) Kir potassium channel subunit expression in retinal glial cells: implications for spatial potassium buffering. Glia 39:292–303PubMedCrossRefGoogle Scholar
  91. Kumar S, Stecher G, Tamura K (2016) MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol Biol Evol 33:1870–1874PubMedCrossRefGoogle Scholar
  92. Lacinova L (2005) Voltage-dependent calcium channels. Gen Physiol Biophys 24(Suppl 1):1–78PubMedGoogle Scholar
  93. Lee A, Fakler B, Kaczmarek LK, Isom LL (2014) More than a pore: ion channel signaling complexes. J Neurosci 34:15159–15169PubMedPubMedCentralCrossRefGoogle Scholar
  94. Liu C, Montell C (2015) Forcing open TRP channels: mechanical gating as a unifying activation mechanism. Biochem Biophys Res Commun 460:22–25PubMedPubMedCentralCrossRefGoogle Scholar
  95. Maroto R, Raso A, Wood TG, Kurosky A, Martinac B, Hamill OP (2005) TRPC1 forms the stretch-activated cation channel in vertebrate cells. Nat Cell Biol 7:179–185PubMedCrossRefGoogle Scholar
  96. Marshall JL, Crosbie-Watson RH (2013) Sarcospan: a small protein with large potential for Duchenne muscular dystrophy. Skelet Muscle 3:1PubMedPubMedCentralCrossRefGoogle Scholar
  97. Matsumura K, Ohlendieck K, Ionasescu VV, Tome FM, Nonaka I, Burghes AH, Mora M, Kaplan JC, Fardeau M, Campbell KP (1993) The role of the dystrophin-glycoprotein complex in the molecular pathogenesis of muscular dystrophies. Neuromuscul Disord 3:533–535PubMedCrossRefGoogle Scholar
  98. McEwen DP, Meadows LS, Chen C, Thyagarajan V, Isom LL (2004) Sodium channel beta1 subunit-mediated modulation of Nav1.2 currents and cell surface density is dependent on interactions with contactin and ankyrin. J Biol Chem 279:16044–16049PubMedCrossRefGoogle Scholar
  99. McNally EM, Ly CT, Kunkel LM (1998a) Human epsilon-sarcoglycan is highly related to alpha-sarcoglycan (adhalin), the limb girdle muscular dystrophy 2D gene. FEBS Lett 422:27–32PubMedCrossRefGoogle Scholar
  100. McNally EM, de Sa Moreira E, Duggan DJ, Bonnemann CG, Lisanti MP, Lidov HG, Vainzof M, Passos-Bueno MR, Hoffman EP, Zatz M, Kunkel LM (1998b) Caveolin-3 in muscular dystrophy. Hum Mol Genet 7:871–877PubMedCrossRefGoogle Scholar
  101. Millay DP, Goonasekera SA, Sargent MA, Maillet M, Aronow BJ, Molkentin JD (2009) Calcium influx is sufficient to induce muscular dystrophy through a TRPC-dependent mechanism. Proc Natl Acad Sci USA 106:19023–19028PubMedCrossRefGoogle Scholar
  102. Miller G, Wang EL, Nassar KL, Peter AK, Crosbie RH (2007) Structural and functional analysis of the sarcoglycan-sarcospan subcomplex. Exp Cell Res 313:639–651PubMedCrossRefGoogle Scholar
  103. Muller CS, Haupt A, Bildl W, Schindler J, Knaus HG, Meissner M, Rammner B, Striessnig J, Flockerzi V, Fakler B, Schulte U (2010) Quantitative proteomics of the Cav2 channel nano-environments in the mammalian brain. Proc Natl Acad Sci USA 107:14950–14957PubMedCrossRefGoogle Scholar
  104. Murphy AC, Young PW (2015) The actinin family of actin cross-linking proteins—a genetic perspective. Cell Biosci 5:49PubMedPubMedCentralCrossRefGoogle Scholar
  105. Nagelhus EA, Horio Y, Inanobe A, Fujita A, Haug FM, Nielsen S, Kurachi Y, Ottersen OP (1999) Immunogold evidence suggests that coupling of K+ siphoning and water transport in rat retinal Muller cells is mediated by a coenrichment of Kir4.1 and AQP4 in specific membrane domains. Glia 26:47–54PubMedCrossRefGoogle Scholar
  106. Neely JD, Amiry-Moghaddam M, Ottersen OP, Froehner SC, Agre P, Adams ME (2001) Syntrophin-dependent expression and localization of Aquaporin-4 water channel protein. Proc Natl Acad Sci USA 98:14108–14113PubMedCrossRefGoogle Scholar
  107. Nei M, Kumar S (2000). Molecular evolution and phylogenetics. Oxford University Press, OxfordGoogle Scholar
  108. Nigro V, Piluso G, Belsito A, Politano L, Puca AA, Papparella S, Rossi E, Viglietto G, Esposito MG, Abbondanza C, Medici N, Molinari AM, Nigro G, Puca GA (1996) Identification of a novel sarcoglycan gene at 5q33 encoding a sarcolemmal 35 kDa glycoprotein. Hum Mol Genet 5:1179–1186PubMedCrossRefGoogle Scholar
  109. Noel G, Belda M, Guadagno E, Micoud J, Klocker N, Moukhles H (2005) Dystroglycan and Kir4.1 coclustering in retinal Muller glia is regulated by laminin-1 and requires the PDZ-ligand domain of Kir4.1. J Neurochem 94:691–702PubMedCrossRefGoogle Scholar
  110. Ong HL, Cheng KT, Liu X, Bandyopadhyay BC, Paria BC, Soboloff J, Pani B, Gwack Y, Srikanth S, Singh BB, Gill DL, Ambudkar IS (2007) Dynamic assembly of TRPC1-STIM1-Orai1 ternary complex is involved in store-operated calcium influx. Evidence for similarities in store-operated and calcium release-activated calcium channel components. J Biol Chem 282:9105–9116PubMedPubMedCentralCrossRefGoogle Scholar
  111. Patel A, Sharif-Naeini R, Folgering JR, Bichet D, Duprat F, Honore E (2010) Canonical TRP channels and mechanotransduction: from physiology to disease states. Pflug Arch 460:571–581CrossRefGoogle Scholar
  112. Pedersen SF, Owsianik G, Nilius B (2005) TRP channels: an overview. Cell Calcium 38:233–252PubMedCrossRefGoogle Scholar
  113. Perez-Reyes E (2003) Molecular physiology of low-voltage-activated t-type calcium channels. Physiol Rev 83:117–161PubMedCrossRefGoogle Scholar
  114. Petitprez S, Zmoos AF, Ogrodnik J, Balse E, Raad N, El-Haou S, Albesa M, Bittihn P, Luther S, Lehnart SE, Hatem SN, Coulombe A, Abriel H (2011) SAP97 and dystrophin macromolecular complexes determine two pools of cardiac sodium channels Nav1.5 in cardiomyocytes. Circ Res 108:294–304PubMedCrossRefGoogle Scholar
  115. Pillers DA, Fitzgerald KM, Duncan NM, Rash SM, White RA, Dwinnell SJ, Powell BR, Schnur RE, Ray PN, Cibis GW, Weleber RG (1999) Duchenne/Becker muscular dystrophy: correlation of phenotype by electroretinography with sites of dystrophin mutations. Hum Genet 105:2–9PubMedCrossRefGoogle Scholar
  116. Piluso G, Mirabella M, Ricci E, Belsito A, Abbondanza C, Servidei S, Puca AA, Tonali P, Puca GA, Nigro V (2000) Gamma1- and gamma2-syntrophins, two novel dystrophin-binding proteins localized in neuronal cells. J Biol Chem 275:15851–15860PubMedCrossRefGoogle Scholar
  117. Quignard JF, Harricane MC, Menard C, Lory P, Nargeot J, Capron L, Mornet D, Richard S (2001) Transient down-regulation of L-type Ca(2+) channel and dystrophin expression after balloon injury in rat aortic cells. Cardiovasc Res 49:177–188PubMedCrossRefGoogle Scholar
  118. Reissner C, Stahn J, Breuer D, Klose M, Pohlentz G, Mormann M, Missler M (2014) Dystroglycan binding to alpha-neurexin competes with neurexophilin-1 and neuroligin in the brain. J Biol Chem 289:27585–27603PubMedPubMedCentralCrossRefGoogle Scholar
  119. Roberts RG, Bobrow M (1998) Dystrophins in vertebrates and invertebrates. Hum Mol Genet 7:589–95PubMedCrossRefGoogle Scholar
  120. Rurak J, Noel G, Lui L, Joshi B, Moukhles H (2007) Distribution of potassium ion and water permeable channels at perivascular glia in brain and retina of the Large(myd) mouse. J Neurochem 103:1940–1953PubMedCrossRefGoogle Scholar
  121. Sabourin J, Lamiche C, Vandebrouck A, Magaud C, Rivet J, Cognard C, Bourmeyster N, Constantin B (2009) Regulation of TRPC1 and TRPC4 cation channels requires an alpha1-syntrophin-dependent complex in skeletal mouse myotubes. J Biol Chem 284:36248–36261PubMedPubMedCentralCrossRefGoogle Scholar
  122. Sadeghi A, Doyle AD, Johnson BD (2002) Regulation of the cardiac L-type Ca2+ channel by the actin-binding proteins alpha-actinin and dystrophin. Am J Physiol Cell Physiol 282:C1502-11PubMedCrossRefGoogle Scholar
  123. Sadoulet-Puccio HM, Khurana TS, Cohen JB, Kunkel LM (1996) Cloning and characterization of the human homologue of a dystrophin related phosphoprotein found at the Torpedo electric organ post-synaptic membrane. Hum Mol Genet 5:489–96PubMedCrossRefGoogle Scholar
  124. Sadoulet-Puccio HM, Rajala M, Kunkel LM (1997) Dystrobrevin and dystrophin: an interaction through coiled-coil motifs. Proc Natl Acad Sci USA 94:12413–12418PubMedCrossRefGoogle Scholar
  125. Sato S, Omori Y, Katoh K, Kondo M, Kanagawa M, Miyata K, Funabiki K, Koyasu T, Kajimura N, Miyoshi T, Sawai H, Kobayashi K, Tani A, Toda T, Usukura J, Tano Y, Fujikado T, Furukawa T (2008) Pikachurin, a dystroglycan ligand, is essential for photoreceptor ribbon synapse formation. Nat Neurosci 11:923–931PubMedCrossRefGoogle Scholar
  126. Satz JS, Philp AR, Nguyen H, Kusano H, Lee J, Turk R, Riker MJ, Hernandez J, Weiss RM, Anderson MG, Mullins RF, Moore SA, Stone EM, Campbell KP (2009) Visual impairment in the absence of dystroglycan. J Neurosci 29:13136–13146PubMedPubMedCentralCrossRefGoogle Scholar
  127. Shy D, Gillet L, Ogrodnik J, Albesa M, Verkerk AO, Wolswinkel R, Rougier JS, Barc J, Essers MC, Syam N, Marsman RF, van Mil AM, Rotman S, Redon R, Bezzina CR, Remme CA, Abriel H (2014) PDZ domain-binding motif regulates cardiomyocyte compartment-specific NaV1.5 channel expression and function. Circulation 130:147–160PubMedCrossRefGoogle Scholar
  128. Simms BA, Zamponi GW (2012) Trafficking and stability of voltage-gated calcium channels. Cell Mol Life Sci 69:843–856PubMedCrossRefGoogle Scholar
  129. Sokolow S, Manto M, Gailly P, Molgo J, Vandebrouck C, Vanderwinden JM, Herchuelz A, Schurmans S (2004) Impaired neuromuscular transmission and skeletal muscle fiber necrosis in mice lacking Na/Ca exchanger 3. J Clin Invest 113:265–273PubMedPubMedCentralCrossRefGoogle Scholar
  130. Spurney CF (2011) Cardiomyopathy of Duchenne muscular dystrophy: current understanding and future directions. Muscle Nerve 44:8–19PubMedCrossRefGoogle Scholar
  131. Staaf S, Maxvall I, Lind U, Husmark J, Mattsson JP, Ernfors P, Pierrou S (2009) Down regulation of TRPC1 by shRNA reduces mechanosensitivity in mouse dorsal root ganglion neurons in vitro. Neurosci Lett 457:3–7PubMedCrossRefGoogle Scholar
  132. Sugita S, Saito F, Tang J, Satz J, Campbell K, Sudhof TC (2001) A stoichiometric complex of neurexins and dystroglycan in brain. J Cell Biol 154:435–445PubMedPubMedCentralCrossRefGoogle Scholar
  133. Taylor PJ, Betts GA, Maroulis S, Gilissen C, Pedersen RL, Mowat DR, Johnston HM, Buckley MF (2010) Dystrophin gene mutation location and the risk of cognitive impairment in Duchenne muscular dystrophy. PLoS ONE 5:e8803PubMedPubMedCentralCrossRefGoogle Scholar
  134. Tozawa T, Itoh K, Yaoi T, Tando S, Umekage M, Dai H, Hosoi H, Fushiki S (2012) The shortest isoform of dystrophin (Dp40) interacts with a group of presynaptic proteins to form a presumptive novel complex in the mouse brain. Mol Neurobiol 45:287–297PubMedPubMedCentralCrossRefGoogle Scholar
  135. Vandebrouck A, Ducret T, Basset O, Sebille S, Raymond G, Ruegg U, Gailly P, Cognard C, Constantin B (2006) Regulation of store-operated calcium entries and mitochondrial uptake by minidystrophin expression in cultured myotubes. Faseb j 20:136–138PubMedCrossRefGoogle Scholar
  136. 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 alpha1-syntrophin: association of TRPC1 with dystrophin complex and the PDZ domain of alpha1-syntrophin. Faseb J 21:608–617CrossRefGoogle Scholar
  137. Vandebrouck C, Duport G, Cognard C, Raymond G (2001) Cationic channels in normal and dystrophic human myotubes. Neuromuscul Disord 11:72–79PubMedCrossRefGoogle Scholar
  138. Vandebrouck C, Martin D, Colson-Van Schoor M, Debaix H, Gailly P (2002) Involvement of TRPC in the abnormal calcium influx observed in dystrophic (mdx) mouse skeletal muscle fibers. J Cell Biol 158:1089–1096PubMedPubMedCentralCrossRefGoogle Scholar
  139. Vazquez G, Wedel BJ, Aziz O, Trebak M, Putney JW Jr (2004) The mammalian TRPC cation channels. Biochim Biophys Acta 1742:21–36PubMedCrossRefGoogle Scholar
  140. Venkatachalam K, Luo J, Montell C (2014) Evolutionarily conserved, multitasking TRP channels: lessons from worms and flies. Handb Exp Pharmacol 223:937–962PubMedPubMedCentralCrossRefGoogle Scholar
  141. Venkatachalam K, Montell C (2007) TRP channels. Annu Rev Biochem 76:387–417PubMedPubMedCentralCrossRefGoogle Scholar
  142. Wheeler MT, Zarnegar S, McNally EM (2002) Zeta-sarcoglycan, a novel component of the sarcoglycan complex, is reduced in muscular dystrophy. Hum Mol Genet 11:2147–2154PubMedCrossRefGoogle Scholar
  143. Woolf PJ, Lu S, Cornford-Nairn R, Watson M, Xiao XH, Holroyd SM, Brown L, Hoey AJ (2006) Alterations in dihydropyridine receptors in dystrophin-deficient cardiac muscle. Am J Physiol Heart Circ Physiol 290:H2439–H2445CrossRefGoogle Scholar
  144. Yeung EW, Whitehead NP, Suchyna TM, Gottlieb PA, Sachs F, Allen DG (2005). Effects of stretch-activated channel blockers on [Ca2+]i and muscle damage in the mdx mouse. J Physiol 562:367–380CrossRefGoogle Scholar
  145. Yoshida M, Ozawa E (1990) Glycoprotein complex anchoring dystrophin to sarcolemma. J Biochem 108:748–752PubMedCrossRefGoogle Scholar
  146. Yu FH, Catterall WA (2003) Overview of the voltage-gated sodium channel family. Genome Biol 4:207PubMedPubMedCentralCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Molecular Biology and Histocompatibility“Dr. Manuel Gea González” General HospitalMexico CityMexico
  2. 2.Faculty of Superior Studies IztacalaNational Autonomous University of Mexico (UNAM)TlalnepantlaMexico
  3. 3.Department of Cell BiologyCenter for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav-IPN)Mexico CityMexico

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