title: Identification of signals that facilitate isoform specific nucleolar localization of myosin IC.
abstract: Myosin IC is a single headed member of the myosin superfamily that localizes to the cytoplasm and the nucleus, where it is involved in transcription by RNA polymerases I and II, intranuclear transport, and nuclear export. In mammalian cells, three isoforms of myosin IC are expressed that differ only in the addition of short isoform-specific N-terminal peptides. Despite the high sequence homology, the isoforms show differences in cellular distribution, in localization to nuclear substructures, and in their interaction with nuclear proteins through yet unknown mechanisms. In this study, we used EGFP-fusion constructs that express truncated or mutated versions of myosin IC isoforms to detect regions that are involved in isoform-specific localization. We identified two nucleolar localization signals (NoLS). One NoLS is located in the myosin IC isoform B specific N-terminal peptide, the second NoLS is located upstream of the neck region within the head domain. We demonstrate that both NoLS are functional and necessary for nucleolar localization of specifically myosin IC isoform B. Our data provide a first mechanistic explanation for the observed functional differences between the myosin IC isoforms and are an important step toward our understanding of the underlying mechanisms that regulate the various and distinct functions of myosin IC isoforms.
authors: Department of Physiology and Biophysics, University at Buffalo-State University of New York, Buffalo, NY, USA.
authors: Ryan S
authors: RS
authors: Schwab
authors: Ivanna
authors: I
authors: Ihnatovych
authors: Sharifah Z S A
authors: SZ
authors: Yunus
authors: Tera
authors: T
authors: Domaradzki
authors: Wilma A
authors: WA
authors: Hofmann
mesh_terms: D000818:Animals; D019556:COS Cells; D002466:Cell Nucleolus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D006801:Humans; D008954:Models, Biological; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D024461:Myosin Type I / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021382:Protein Sorting Signals / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D021381:Protein Transport / Q000235:genetics; D013379:Substrate Specificity; D014162:Transfection
chemical_list: D050505:Mutant Proteins; D020033:Protein Isoforms; D021382:Protein Sorting Signals; D024461:Myosin Type I; C460367:MYO1C protein, human