Nuclear localization of Myomesin-1: possible functions.
Myomesin-I (also known as Skelemin) is a approximately 185 kDa protein, which is highly expressed in striated muscle. It contains the prototypic class-I (type-III fibronectin) and class-II (C2-immunoglobulin) motifs. Previous studies have shown the presence of Myomesin-I at the M-line of the sarcomere, where it is thought to interact with thick filament constituents. As reported previously, Myomesin-I was localized to the M-line in the adult cardiac myocytes (adult-myocytes). However, we found that Myomesin-I was also present exclusively in the nucleus of myocytes isolated from new born pups (neonatal-myocytes). In addition, the ectopically expressed Myomesin-I was primarily targeted to the nucleus, similar to the neonatal myocytes. Further investigations revealed that the nuclear-targeting signals were present within the N-terminal 256 residues. A strong consensus sequence for sumoylation is present within the N-terminal 256 residues and is implicated in the shuttling of Myomesin-I between nucleus and cytoplasm. Gene array analysis showed that the presence of Myomesin-I in the nucleus led to the differential expression of more than 42 genes. These studies show a novel and previously unknown localization and function for Myomesin-I.
Reddy
Kumar B
KB
Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue #NB5, Cleveland, OH 44195, USA. reddyk@ccf.org
Fox
Joan E B
JE
Price
Maureen G
MG
Kulkarni
Sucheta
S
Gupta
Sudhiranjan
S
Das
Biswajit
B
Smith
Dawn M
DM
D000818:Animals; D000831:Animals, Newborn; D016466:CHO Cells; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D064211:Connectin; D006224:Cricetinae; D003412:Cricetulus; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D015536:Down-Regulation; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012518:Sarcomeres / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation
D064211:Connectin; D003598:Cytoskeletal Proteins; D009124:Muscle Proteins; C577300:Myom1 protein, mouse; C577286:Myom1 protein, rat