title: Aciculin interacts with filamin C and Xin and is essential for myofibril assembly, remodeling and maintenance.
abstract: Filamin C (FLNc) and Xin actin-binding repeat-containing proteins (XIRPs) are multi-adaptor proteins that are mainly expressed in cardiac and skeletal muscles and which play important roles in the assembly and repair of myofibrils and their attachment to the membrane. We identified the dystrophin-binding protein aciculin (also known as phosphoglucomutase-like protein 5, PGM5) as a new interaction partner of FLNc and Xin. All three proteins colocalized at intercalated discs of cardiac muscle and myotendinous junctions of skeletal muscle, whereas FLNc and aciculin also colocalized in mature Z-discs. Bimolecular fluorescence complementation experiments in developing cultured mammalian skeletal muscle cells demonstrated that Xin and aciculin also interact in FLNc-containing immature myofibrils and areas of myofibrillar remodeling and repair induced by electrical pulse stimulation (EPS). Fluorescence recovery after photobleaching (FRAP) experiments showed that aciculin is a highly dynamic and mobile protein. Aciculin knockdown in myotubes led to failure in myofibril assembly, alignment and membrane attachment, and a massive reduction in myofibril number. A highly similar phenotype was found upon depletion of aciculin in zebrafish embryos. Our results point to a thus far unappreciated, but essential, function of aciculin in myofibril formation, maintenance and remodeling.
authors: Institute for Cell Biology, University of Bonn, 53121 Bonn, Germany.
authors: Sibylle
authors: S
authors: Molt
authors: Department of Internal Medicine II, University of Ulm, 89081 Ulm, Germany.
authors: John B
authors: JB
authors: Bührdel
authors: University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors: Sergiy
authors: S
authors: Yakovlev
authors: Institute for Cell Biology, University of Bonn, 53121 Bonn, Germany.
authors: Peter
authors: P
authors: Schein
authors: Institute for Cell Biology, University of Bonn, 53121 Bonn, Germany.
authors: Zacharias
authors: Z
authors: Orfanos
authors: Institute for Cell Biology, University of Bonn, 53121 Bonn, Germany.
authors: Gregor
authors: G
authors: Kirfel
authors: Department of Biochemistry and Molecular Cell Biology, Max F. Perutz Laboratories, University of Vienna, 1030 Vienna, Austria.
authors: Lilli
authors: L
authors: Winter
authors: Department of Biochemistry and Molecular Cell Biology, Max F. Perutz Laboratories, University of Vienna, 1030 Vienna, Austria.
authors: Gerhard
authors: G
authors: Wiche
authors: Institute for Cell Biology, University of Bonn, 53121 Bonn, Germany.
authors: Peter F M
authors: PF
authors: van der Ven
authors: Department of Internal Medicine II, University of Ulm, 89081 Ulm, Germany.
authors: Wolfgang
authors: W
authors: Rottbauer
authors: Department of Internal Medicine II, University of Ulm, 89081 Ulm, Germany.
authors: Steffen
authors: S
authors: Just
authors: University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors: Alexey M
authors: AM
authors: Belkin
authors: Institute for Cell Biology, University of Bonn, 53121 Bonn, Germany dfuerst@uni-bonn.de.
authors: Dieter O
authors: DO
authors: Fürst
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D064448:Filamins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032446:Myoblasts / Q000378:metabolism; D009210:Myofibrils / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010733:Phosphoglucomutase / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D064448:Filamins; D009687:Nuclear Proteins; C484255:PGM5 protein, human; C090710:Pgm5 protein, mouse; C512114:XIRP1 protein, human; C118478:Xin protein, mouse; D010733:Phosphoglucomutase
keywords: Aciculin; Myofibrillogenesis; PGM5; Phosphoglucomutase; Striated muscle; XIRP1; Xin actin-binding repeat-containing protein