title: Obscurin determines the architecture of the longitudinal sarcoplasmic reticulum.
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.
authors: Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors: Stephan
authors: S
authors: Lange
authors: Kunfu
authors: K
authors: Ouyang
authors: Gretchen
authors: G
authors: Meyer
authors: Li
authors: L
authors: Cui
authors: Hongqiang
authors: H
authors: Cheng
authors: Richard L
authors: RL
authors: Lieber
authors: Ju
authors: J
authors: Chen
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000235:genetics / Q000378:metabolism; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D053595:Embryonic Stem Cells / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000502:physiology*; D047468:Immunoprecipitation; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000502:physiology*; D018482:Muscle, Skeletal / Q000648:ultrastructure*; D032446:Myoblasts / Q000378:metabolism; D000075687:NEDD8 Protein; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064067:Rho Guanine Nucleotide Exchange Factors; D012519:Sarcoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism
chemical_list: C491707:Ank1 protein, mouse; D017487:Ankyrins; D020662:Guanine Nucleotide Exchange Factors; D009124:Muscle Proteins; D000075687:NEDD8 Protein; C513172:Nedd8 protein, mouse; D012333:RNA, Messenger; D064067:Rho Guanine Nucleotide Exchange Factors; D025801:Ubiquitin; D014452:Ubiquitins; D017346:Protein Serine-Threonine Kinases; C515766:obscn protein, mouse