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A signaling hub of insulin receptor, dystrophin glycoprotein complex and plakoglobin regulates muscle size
by
Ayalon, Bar
, Dahan, Nitsan
, Eid Mutlak, Yara
, Volodin, Alexandra
, Aweida, Dina
, Parnis, Anna
, Cohen, Shenhav
in
13/44
/ 13/95
/ 14/19
/ 14/34
/ 42/70
/ 631/80
/ 631/80/304
/ 64/60
/ 82/1
/ 82/29
/ 82/58
/ 96/63
/ Animals
/ Atrophy
/ Autophagy
/ Catenin
/ Cell growth
/ Cell Membrane - metabolism
/ Disease Models, Animal
/ Duchenne's muscular dystrophy
/ Dystroglycan
/ Dystroglycans - metabolism
/ Dystrophin
/ Dystrophin - genetics
/ Dystrophin - metabolism
/ Dystrophy
/ gamma Catenin - metabolism
/ Glycoproteins
/ Glycoproteins - metabolism
/ Humanities and Social Sciences
/ Insulin
/ Insulin resistance
/ Male
/ Masking
/ Metabolism
/ Mice
/ Mice, Transgenic
/ Microscopy
/ multidisciplinary
/ Muscle, Skeletal - metabolism
/ Muscles
/ Muscular dystrophy
/ Muscular Dystrophy, Duchenne - metabolism
/ Mutation
/ Physiology
/ Protein Domains
/ Protein purification
/ Protein turnover
/ Proteins
/ Purification
/ Receptor, Insulin - metabolism
/ Science
/ Science (multidisciplinary)
/ Signal Transduction
/ Signaling
/ Skeletal muscle
/ Transgenic mice
2020
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A signaling hub of insulin receptor, dystrophin glycoprotein complex and plakoglobin regulates muscle size
by
Ayalon, Bar
, Dahan, Nitsan
, Eid Mutlak, Yara
, Volodin, Alexandra
, Aweida, Dina
, Parnis, Anna
, Cohen, Shenhav
in
13/44
/ 13/95
/ 14/19
/ 14/34
/ 42/70
/ 631/80
/ 631/80/304
/ 64/60
/ 82/1
/ 82/29
/ 82/58
/ 96/63
/ Animals
/ Atrophy
/ Autophagy
/ Catenin
/ Cell growth
/ Cell Membrane - metabolism
/ Disease Models, Animal
/ Duchenne's muscular dystrophy
/ Dystroglycan
/ Dystroglycans - metabolism
/ Dystrophin
/ Dystrophin - genetics
/ Dystrophin - metabolism
/ Dystrophy
/ gamma Catenin - metabolism
/ Glycoproteins
/ Glycoproteins - metabolism
/ Humanities and Social Sciences
/ Insulin
/ Insulin resistance
/ Male
/ Masking
/ Metabolism
/ Mice
/ Mice, Transgenic
/ Microscopy
/ multidisciplinary
/ Muscle, Skeletal - metabolism
/ Muscles
/ Muscular dystrophy
/ Muscular Dystrophy, Duchenne - metabolism
/ Mutation
/ Physiology
/ Protein Domains
/ Protein purification
/ Protein turnover
/ Proteins
/ Purification
/ Receptor, Insulin - metabolism
/ Science
/ Science (multidisciplinary)
/ Signal Transduction
/ Signaling
/ Skeletal muscle
/ Transgenic mice
2020
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A signaling hub of insulin receptor, dystrophin glycoprotein complex and plakoglobin regulates muscle size
by
Ayalon, Bar
, Dahan, Nitsan
, Eid Mutlak, Yara
, Volodin, Alexandra
, Aweida, Dina
, Parnis, Anna
, Cohen, Shenhav
in
13/44
/ 13/95
/ 14/19
/ 14/34
/ 42/70
/ 631/80
/ 631/80/304
/ 64/60
/ 82/1
/ 82/29
/ 82/58
/ 96/63
/ Animals
/ Atrophy
/ Autophagy
/ Catenin
/ Cell growth
/ Cell Membrane - metabolism
/ Disease Models, Animal
/ Duchenne's muscular dystrophy
/ Dystroglycan
/ Dystroglycans - metabolism
/ Dystrophin
/ Dystrophin - genetics
/ Dystrophin - metabolism
/ Dystrophy
/ gamma Catenin - metabolism
/ Glycoproteins
/ Glycoproteins - metabolism
/ Humanities and Social Sciences
/ Insulin
/ Insulin resistance
/ Male
/ Masking
/ Metabolism
/ Mice
/ Mice, Transgenic
/ Microscopy
/ multidisciplinary
/ Muscle, Skeletal - metabolism
/ Muscles
/ Muscular dystrophy
/ Muscular Dystrophy, Duchenne - metabolism
/ Mutation
/ Physiology
/ Protein Domains
/ Protein purification
/ Protein turnover
/ Proteins
/ Purification
/ Receptor, Insulin - metabolism
/ Science
/ Science (multidisciplinary)
/ Signal Transduction
/ Signaling
/ Skeletal muscle
/ Transgenic mice
2020
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A signaling hub of insulin receptor, dystrophin glycoprotein complex and plakoglobin regulates muscle size
Journal Article
A signaling hub of insulin receptor, dystrophin glycoprotein complex and plakoglobin regulates muscle size
2020
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Overview
Signaling through the insulin receptor governs central physiological functions related to cell growth and metabolism. Here we show by tandem native protein complex purification approach and super-resolution STED microscopy that insulin receptor activity requires association with the fundamental structural module in muscle, the dystrophin glycoprotein complex (DGC), and the desmosomal component plakoglobin (γ-catenin). The integrity of this high-molecular-mass assembly renders skeletal muscle susceptibility to insulin, because DGC-insulin receptor dissociation by plakoglobin downregulation reduces insulin signaling and causes atrophy. Furthermore, low insulin receptor activity in muscles from transgenic or fasted mice decreases plakoglobin-DGC-insulin receptor content on the plasma membrane, but not when plakoglobin is overexpressed. By masking β-dystroglycan LIR domains, plakoglobin prevents autophagic clearance of plakoglobin-DGC-insulin receptor co-assemblies and maintains their function. Our findings establish DGC as a signaling hub, and provide a possible mechanism for the insulin resistance in Duchenne Muscular Dystrophy, and for the cardiomyopathies seen with plakoglobin mutations.
Insulin receptor signaling governs central physiological functions related to cell growth and metabolism. Here the authors use protein complex purification and super-resolution microscopy to show that insulin receptor activity requires association with dystrophin glycoprotein complex and plakoglobin.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/95
/ 14/19
/ 14/34
/ 42/70
/ 631/80
/ 64/60
/ 82/1
/ 82/29
/ 82/58
/ 96/63
/ Animals
/ Atrophy
/ Catenin
/ Duchenne's muscular dystrophy
/ Humanities and Social Sciences
/ Insulin
/ Male
/ Masking
/ Mice
/ Muscle, Skeletal - metabolism
/ Muscles
/ Muscular Dystrophy, Duchenne - metabolism
/ Mutation
/ Proteins
/ Receptor, Insulin - metabolism
/ Science
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