Abstract
The giant protein obscurin is thought to link the sarcomere with the sarcoplasmic reticulum (SR). The N-terminus of obscurin interacts with the M-band proteins titin and myomesin, whereas the C-terminus mediates interactions with ankyrin proteins. Here, we investigate the importance of obscurin for SR architecture and organization. Lack of obscurin in cross-striated muscles leads to changes in longitudinal SR architecture and disruption of small ankyrin-1.5 (sAnk1.5) expression and localization. Changes in SR architecture in obscurin knockout mice are also associated with alterations in several SR or SR-associated proteins, such as ankyrin-2 and beta-spectrin. Finally, obscurin knockout mice display centralized nuclei in skeletal muscles as a sign of mild myopathy, but have normal sarcomeric structure and preserved muscle function.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Ankyrins / genetics
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Ankyrins / metabolism
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COS Cells
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Cells, Cultured
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Chlorocebus aethiops
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Embryonic Stem Cells / metabolism
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Guanine Nucleotide Exchange Factors / physiology*
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Immunoprecipitation
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Mice
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Mice, Knockout
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Muscle Proteins / physiology*
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Muscle, Skeletal / ultrastructure*
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Myoblasts / metabolism
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NEDD8 Protein
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Protein Serine-Threonine Kinases
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Rho Guanine Nucleotide Exchange Factors
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Sarcoplasmic Reticulum / metabolism*
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Sarcoplasmic Reticulum / ultrastructure
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Transfection
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Ubiquitin / metabolism
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Ubiquitins / genetics
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Ubiquitins / metabolism
Substances
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Ank1 protein, mouse
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Ankyrins
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Guanine Nucleotide Exchange Factors
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Muscle Proteins
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NEDD8 Protein
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Nedd8 protein, mouse
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RNA, Messenger
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Rho Guanine Nucleotide Exchange Factors
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Ubiquitin
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Ubiquitins
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Protein Serine-Threonine Kinases
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obscn protein, mouse