Aciculin interacts with filamin C and Xin and is essential for myofibril assembly, remodeling and maintenance

• Published in: Journal of cell science Vol. 127; no. Pt 16; pp. 3578 - 3592
• Main Authors: Molt, Sibylle, Bührdel, John B, Yakovlev, Sergiy, Schein, Peter, Orfanos, Zacharias, Kirfel, Gregor, Winter, Lilli, Wiche, Gerhard, van der Ven, Peter F M, Rottbauer, Wolfgang, Just, Steffen, Belkin, Alexey M, Fürst, Dieter O
• Format: Journal Article
• Language: English
• Published: England 15.08.2014
• Subjects: Animals; Cell Line; Cells, Cultured; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Filamins - genetics; Filamins - metabolism; Humans; Mice; Mice, Inbred C57BL; Mice, Knockout; Myoblasts - metabolism; Myofibrils - genetics; Myofibrils - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Phosphoglucomutase - genetics; Phosphoglucomutase - metabolism; Protein Binding; Aciculin; XIRP1; Myofibrillogenesis; PGM5; Striated muscle; Xin actin-binding repeat-containing protein; Phosphoglucomutase
• DOI: 10.1242/jcs.152157
• ISSN: 0021-9533

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.