Biochemical and Functional Interplay Between Ion Channels and the Components of the Dystrophin-Associated Glycoprotein Complex
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.
KeywordsDGC 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.
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Conflict of interest
The authors declare that they have no conflicts of interest.
- 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
- 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
- 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
- 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
- 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
- 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
- Holland PW, Garcia-Fernandez J, Williams NA, Sidow A (1994). Gene duplications and the origins of vertebrate development. Dev Suppl 1994:125–133Google Scholar
- 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
- 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
- Nei M, Kumar S (2000). Molecular evolution and phylogenetics. Oxford University Press, OxfordGoogle Scholar
- 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
- 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
- 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
- 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
- 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
- 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