The 16 kDa subunit of vacuolar H+-ATPase is a novel sarcoglycan-interacting protein
Autor: | Mhairi A. Skinner, Qian-Chun Yu, Weixing Shi, Alan G. Wildeman, Yiu-mo Michael Chan, Jiwei Chen |
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Rok vydání: | 2006 |
Předmět: |
musculoskeletal diseases
Male congenital hereditary and neonatal diseases and abnormalities Vacuolar Proton-Translocating ATPases BIO14.6 hamster Protein subunit Integrin Muscle Fibers Skeletal Biology Cell Line Mice Sarcolemma Cricetinae Sarcoglycans Chlorocebus aethiops medicine Animals Muscular dystrophy Sarcoglycan Microscopy Immunoelectron Muscle Skeletal Molecular Biology Myogenesis Integrin beta1 Cell Membrane musculoskeletal system medicine.disease Cell biology Transmembrane domain Protein Subunits Biochemistry biology.protein Molecular Medicine 16K Vacuolar ATPase Protein Binding Signal Transduction |
Zdroj: | Biochimica et biophysica acta. 1772(5) |
ISSN: | 0006-3002 |
Popis: | The sarcoglycan complex in muscle consists of alpha-, beta-, gamma- and delta-sarcoglycan and is part of the larger dystrophin-glycoprotein complex (DGC), which is essential for maintaining muscle membrane integrity. Mutations in any of the four sarcoglycans cause limb-girdle muscular dystrophies (LGMD). In this report, we have identified a novel interaction between delta-sarcoglycan and the 16 kDa subunit c (16K) of vacuolar H(+)-ATPase. Co-expression studies in heterologous cell system revealed that 16K interacts specifically with delta-sarcoglycan and the highly related gamma-sarcoglycan through the transmembrane domains. In cultured C2C12 myotubes, 16K forms a complex with sarcoglycans at the plasma membrane. Loss of sarcoglycans in the sarcoglycan-deficient BIO14.6 hamster destabilizes the DGC and alters the localization of 16K at the sarcolemma. In addition, the steady state level of beta(1)-integrin is increased. Recent studies have shown that 16K also interacts directly with beta(1)-integrin and our data demonstrated that sarcoglycans, 16K and beta(1)-integrin were immunoprecipitated together in C2C12 myotubes. Since sarcoglycans have been proposed to participate in bi-directional signaling with integrins, our findings suggest that 16K might mediate the communication between sarcoglycans and integrins and play an important role in the pathogenesis of muscular dystrophy. |
Databáze: | OpenAIRE |
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