The molecular cross talk of the dystrophin–glycoprotein complex

Gawor, Marta; Prószyński, Tomasz J.

doi:10.1111/nyas.13500

Cited by 52 publications

(30 citation statements)

References 116 publications

(158 reference statements)

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“…It is therefore not surprising that abnormal quaternary protein structures and impaired protein complex formation are involved in the molecular mechanisms that underlie various disease mechanisms. A representative example of a collapsed protein complex being the disease initiator of a multifaceted pathological process is the loss of the dystrophin‐glycoprotein complex in the highly progressive neuromuscular disorder Duchenne muscular dystrophy . The primary abnormality in the Dmd gene causes the almost complete loss of its full‐length protein product, the Dp427 isoform of the membrane cytoskeletal protein dystrophin , and concomitant reduction in all members of the core dystrophin‐associated glycoprotein complex .…”

Section: Introductionmentioning

confidence: 99%

Comparative gel‐based proteomic analysis of chemically crosslinked complexes in dystrophic skeletal muscle

et al. 2018

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Duchenne muscular dystrophy is a highly progressive muscle wasting disease with a complex pathophysiology that is based on primary abnormalities in the dystrophin gene. In order to study potential changes in the oligomerization of high‐molecular‐mass protein complexes in dystrophic skeletal muscle, chemical crosslinking was combined with mass spectrometric analysis. The biochemical stabilization of protein interactions was carried out with the homo‐bifunctional and amine‐reactive agent bis[sulfosuccinimidyl]suberate, followed by protein shift analysis in one‐dimensional gels. The proteomic approach identified 11 and 15 protein species in wild type versus dystrophic microsomal fractions, respectively, as well as eight common proteins, with an electrophoretic mobility shift to very high molecular mass following chemical crosslinking. In dystrophin‐deficient preparations, several protein species with an increased tendency of oligomerisation were identified as components of the sarcolemma and its associated intra‐ and extracellular structures, as well as mitochondria. This included the sarcolemmal proteins myoferlin and caveolin, the cytoskeletal components vimentin and tubulin, extracellular collagen alpha‐1(XII) and the mitochondrial trifunctional enzyme and oxoglutarate dehydrogenase. These changes are probably related to structural and metabolic adaptations, especially cellular repair processes, which agrees with the increased oligomerisation of myosin‐3, myosin‐9 and actin, and their role in cellular regeneration and structural adjustments in dystrophinopathy.

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Section: Introductionmentioning

confidence: 99%

Comparative gel‐based proteomic analysis of chemically crosslinked complexes in dystrophic skeletal muscle

et al. 2018

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“…PTPN21 PY12 and PTPN14-PY12 bind to KIBRA WW tandem with essentially the same affinity (Kd ~8 nM), as the sequences of these two peptides are very similar. Interestingly, β-Dystroglycan, a protein known to play critical roles in Hippo signaling-related cell adhesion and cell growth (Morikawa et al, 2017, Gawor andProszynski, 2018), can also bind to KIBRA WW tandem with high affinity (Kd ~96 nM, Fig. 7E).…”

Section: Identification Of New Binders Of the Kibra And Magi2/3 Ww Tamentioning

confidence: 96%

Decoding WW Domain Tandem-mediated Target Recognitions in Tissue Growth and Cell Polarity

Lin

Zhou

Xie

et al. 2019

Preprint

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WW domain tandem-containing proteins such as KIBRA, YAP, and MAGI play critical roles in cell growth and polarity via binding to and positioning target proteins in specific subcellular regions. An immense disparity exists between promiscuity of WW domain-mediated target bindings and specific roles of WW domain scaffold proteins in cell growth regulation. Here, we discovered that WW domain tandems of KIBRA and MAGI, but not YAP, bind to specific target proteins with extremely high affinity and exquisite specificity. Via systematic structural biology and biochemistry approaches, we decoded the target binding rules of WW domain tandems from cell growth regulatory proteins and uncovered a list of previously unknown WW tandem binding proteins such as β-Dystroglycan, JCAD, and PTPN21. The WW tandemmediated target recognition mechanisms elucidated here can guide functional studies of WW domain proteins in cell growth and polarity as well as in other cellular processes including neuronal synaptic signaling.

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“…The major ECM receptors contain integrin complexes and the dystrophin-associated glycoprotein complex [16][17][18] . These protein assemblies stabilize postsynaptic components and provide a platform for the recruitment of signaling molecules that regulate postsynaptic specialization 17,19 . Muscle cells form a thick ECM around the fiber that contains various laminins, collagens, fibronectin, and other glycoproteins 20 .…”

Section: Introductionmentioning

confidence: 99%

An improved method for culturing myotubes on laminins for the robust clustering of postsynaptic machinery

Pęziński¹,

Daszczuk

Pradhan³

et al. 2019

Preprint

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Motor neurons form specialized synapses with skeletal muscle fibers, called neuromuscular junctions (NMJs). Cultured myotubes are used as a simplified in vitro system to study the postsynaptic specialization of muscles. The stimulation of myotubes with the glycoprotein agrin or laminin-111 induces the clustering of postsynaptic machinery that contains acetylcholine receptors (AChRs). When myotubes are grown on laminin-coated surfaces, AChR clusters undergo developmental remodeling to form topologically complex structures that resemble mature NMJs. Needing further exploration are the molecular processes that govern AChR cluster assembly and its developmental maturation. Here, we describe an improved protocol for culturing muscle cells to promote the formation of complex AChR clusters. We screened various laminin isoforms and showed that laminin-221 was the most potent for inducing AChR clusters, whereas laminin-121, laminin-211, and laminin-221 afforded the highest percentages of topologically complex assemblies. Human primary myotubes that were formed by myoblasts obtained from patient biopsies also assembled AChR clusters that underwent remodeling in vitro. Collectively, these results demonstrate an advancement of culturing myotubes that can facilitate high-throughput screening for potential therapeutic targets for neuromuscular disorders.

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The molecular cross talk of the dystrophin–glycoprotein complex

Cited by 52 publications

References 116 publications

Comparative gel‐based proteomic analysis of chemically crosslinked complexes in dystrophic skeletal muscle

Comparative gel‐based proteomic analysis of chemically crosslinked complexes in dystrophic skeletal muscle

Decoding WW Domain Tandem-mediated Target Recognitions in Tissue Growth and Cell Polarity

An improved method for culturing myotubes on laminins for the robust clustering of postsynaptic machinery

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