Role of the RNA-binding protein IMP-2 in muscle cell motility.
Insulin-like growth factor 2 (IGF-2) mRNA-binding proteins (IMPs) are a family of posttranscriptional regulatory factors with well-understood roles in embryonic development and cancer but with poorly characterized functions in normal adult cells and tissues. We now show that IMP-2, the most ubiquitously expressed member of the family, is abundant in human and mouse adult skeletal myoblasts, where it is indispensable for cell motility and for stabilization of microtubules. To explore the functions of IMP-2, we analyzed the transcripts that were differentially regulated in IMP-2-depleted myoblasts and bound to IMP-2 in normal myoblasts. Among them were the mRNAs of PINCH-2, an important mediator of cell adhesion and motility, and MURF-3, a microtubule-stabilizing protein. By gain- and loss-of-function assays and gel shift experiments, we show that IMP-2 regulates the expression of PINCH-2 and MURF-3 proteins via direct binding to their mRNAs. Upregulation of PINCH-2 in IMP-2-depleted myoblasts is the key event responsible for their decreased motility. Our data reveal how the posttranscriptional regulation of gene expression by IMP-2 contributes to the control of adhesion structures and stable microtubules and demonstrate an important function for IMP-2 in cellular motility.
Université Paris-Sud, Villejuif, France.
Selim
S
Boudoukha
Sylvain
S
Cuvellier
Anna
A
Polesskaya
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D060588:LIM Domain Proteins; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D032342:Muscle Cells / Q000166:cytology / Q000502:physiology*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C498779:IGF2BP2 protein, human; D060588:LIM Domain Proteins; C490235:LIMS2 protein, human; D008565:Membrane Proteins; D009124:Muscle Proteins; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; C413644:Rnf30 protein, mouse; D014404:Tubulin