Nonmuscle myosin-dependent synthesis of Type I collagen

Le Cai, Dillon Fritz, Lela Stefanovic, Branko Stefanovic*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    28 Scopus citations

    Abstract

    Type I collagen, synthesized in all tissues as the heterotrimer of two α1(I) polypeptides and one α2(I) polypeptide, is the most abundant protein in the human body. Here we show that intact nonmuscle myosin filaments are required for the synthesis of heterotrimeric type I collagen. Conserved 5α stem-loop in collagen α1(I) and α2(I) mRNAs binds the RNA-binding protein LARP6. LARP6 interacts with nonmuscle myosin through its C-terminal domain and associates collagen mRNAs with the filaments. Dissociation of nonmuscle myosin filaments results in secretion of collagen α1(I) homotrimer, diminished intracellular colocalization of collagen α1(I) and α2(I) polypeptides (required for folding of the heterotrimer), and their increased intracellular degradation. Inhibition of the motor function of myosin has similar collagen-specific effects, while disruption of actin filaments has a general effect on protein secretion. Nonmuscle myosin copurifies with polysomes, and there is a subset of polysomes involved in myosin-dependent translation of collagen mRNAs. These results indicate that association of collagen mRNAs with nonmuscle myosin filaments is necessary to coordinately synthesize collagen α1(I) and α2(I) polypeptides. We postulate that LARP6/myosin-dependent mechanism regulates the synthesis of heterotrimeric type I collagen by coordinating the translation of collagen mRNAs.

    Original languageEnglish (US)
    Pages (from-to)564-578
    Number of pages15
    JournalJournal of Molecular Biology
    Volume401
    Issue number4
    DOIs
    StatePublished - Aug 1 2010

    Keywords

    • LARP6
    • Nonmuscle myosin
    • Translation
    • Type I collagen

    ASJC Scopus subject areas

    • Structural Biology
    • Molecular Biology

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