title: Calcium-regulated import of myosin IC into the nucleus.
abstract: Myosin IC is a molecular motor involved in intracellular transport, cell motility, and transcription. Its mechanical properties are regulated by calcium via calmodulin binding, and its functions in the nucleus depend on import from the cytoplasm. The import has recently been shown to be mediated by the nuclear localization signal located within the calmodulin-binding domain. In the present paper, it is demonstrated that mutations in the calmodulin-binding sequence shift the intracellular distribution of myosin IC to the nucleus. The redistribution is displayed by isoform B, described originally as the "nuclear myosin," but is particularly pronounced with isoform C, the normally cytoplasmic isoform. Furthermore, experimental elevation of the intracellular calcium concentration induces a rapid import of myosin into the nucleus. The import is blocked by the importin β inhibitor importazole. These findings are consistent with a mechanism whereby calmodulin binding prevents recognition of the nuclear localization sequence by importin β, and the steric inhibition of import is released by cell signaling leading to the intracellular calcium elevation. The results establish a mechanistic connection between the calcium regulation of the motor function of myosin IC in the cytoplasm and the induction of its import into the nucleus. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Physiology and Biophysics, University at Buffalo-State University of New York, Buffalo, New York.
authors.forename: Ivan V
authors.initials: IV
authors.lastname: Maly
authors.affiliation: Department of Physiology and Biophysics, University at Buffalo-State University of New York, Buffalo, New York.
authors.forename: Wilma A
authors.initials: WA
authors.lastname: Hofmann
mesh_terms: D020013:Calcium Signaling; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000201:enzymology* / Q000235:genetics; D003593:Cytoplasm / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D024461:Myosin Type I / Q000235:genetics / Q000378:metabolism*; D011799:Quinazolines / Q000494:pharmacology; D028961:beta Karyopherins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D011799:Quinazolines; D028961:beta Karyopherins; C568452:importazole; D024461:Myosin Type I; C460367:MYO1C protein, human
keywords: calcium; calmodulin; importazole; importin; nuclear localization signal