Journal article Open Access

Alternatively spliced N-terminal exons in tropomyosin isoforms do not act as autonomous targeting signals

Martin, Claire; Schevzov, Galina; Gunning, Peter

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  "DOI": "10.1016/j.jsb.2009.12.016", 
  "author": [
      "family": "Martin, Claire"
      "family": "Schevzov, Galina"
      "family": "Gunning, Peter"
  "issued": {
    "date-parts": [
  "abstract": "Tropomyosin (Tm) polymerises head-to-tail to form a continuous polymer located in the major groove of\nthe actin filament. Multiple Tm isoforms are generated by alternative splicing of four genes, and individual\nisoforms show specific localisation patterns in many cell types, and can have differing effects on the\nactin cytoskeleton. Fluorescently-tagged Tm isoforms and mutants were expressed in C2C12 cells to\ninvestigate the mechanisms of alternative localisation of high molecular weight (HMW) and low molecular\nweight (LMW) Tms. Fluorescently-tagged Tm constructs show similar localisation to endogenous\nTms as observed by antibodies, with the HMW Tm3 relatively diminished at the periphery of cells compared\nto LMW isoforms Tm5b or Tm5NM1. Tm3 and Tm5b only differ in their N-terminal exons, but these\nN-terminal exons do not independently direct localisation within the cell, as chimeric mutants Tm3\u2013\nTm5NM1 and Tm5b\u2013Tm5NM1 show an increased peripheral localisation similar to Tm5NM1. The lower\nabundance of Tm3 at the periphery of the cell is not a result of different protein dynamics, as Tm3 and\nTm5b show similar recovery after photobleaching. The relative exclusion of Tm3 from the periphery of\ncells does, however, require interaction with the actin filament, as mutants with truncations at either\nthe N-terminus or the C-terminus are unable to localise to actin stress fibres, and are present in the most\nperipheral regions of the cell. We conclude that it is the entire Tm molecule which is the unit of sorting,\nand that the alternatively spliced N-terminal exons do not act as autonomous targeting signals.", 
  "title": "Alternatively spliced N-terminal exons in tropomyosin isoforms do not act as autonomous targeting signals", 
  "type": "article-journal", 
  "id": "848856"
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