RT Journal Article SR Electronic T1 The myosin-interacting protein SMYD1 is essential for sarcomere organization JF Journal of Cell Science JO J. Cell Sci. FD The Company of Biologists Ltd SP 3127 OP 3136 DO 10.1242/jcs.084772 VO 124 IS 18 A1 Just, Steffen A1 Meder, Benjamin A1 Berger, Ina M. A1 Etard, Christelle A1 Trano, Nicole A1 Patzel, Eva A1 Hassel, David A1 Marquart, Sabine A1 Dahme, Tillman A1 Vogel, Britta A1 Fishman, Mark C. A1 Katus, Hugo A. A1 Strähle, Uwe A1 Rottbauer, Wolfgang YR 2011 UL http://jcs.biologists.org/content/124/18/3127.abstract AB Assembly, maintenance and renewal of sarcomeres require highly organized and balanced folding, transport, modification and degradation of sarcomeric proteins. However, the molecules that mediate these processes are largely unknown. Here, we isolated the zebrafish mutant flatline (fla), which shows disturbed sarcomere assembly exclusively in heart and fast-twitch skeletal muscle. By positional cloning we identified a nonsense mutation within the SET- and MYND-domain-containing protein 1 gene (smyd1) to be responsible for the fla phenotype. We found SMYD1 expression to be restricted to the heart and fast-twitch skeletal muscle cells. Within these cell types, SMYD1 localizes to both the sarcomeric M-line, where it physically associates with myosin, and the nucleus, where it supposedly represses transcription through its SET and MYND domains. However, although we found transcript levels of thick filament chaperones, such as Hsp90a1 and UNC-45b, to be severely upregulated in fla, its histone methyltransferase activity – mainly responsible for the nuclear function of SMYD1 – is dispensable for sarcomerogenesis. Accordingly, sarcomere assembly in fla mutant embryos can be reconstituted by ectopically expressing histone methyltransferase-deficient SMYD1. By contrast, ectopic expression of myosin-binding-deficient SMYD1 does not rescue fla mutants, implicating an essential role for the SMYD1–myosin interaction in cardiac and fast-twitch skeletal muscle thick filament assembly.