Nonmuscle myosin-dependent synthesis of type I collagen.
Type I collagen, synthesized in all tissues as the heterotrimer of two alpha1(I) polypeptides and one alpha2(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 5' stem-loop in collagen alpha1(I) and alpha2(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 alpha1(I) homotrimer, diminished intracellular colocalization of collagen alpha1(I) and alpha2(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 alpha1(I) and alpha2(I) polypeptides. We postulate that LARP6/myosin-dependent mechanism regulates the synthesis of heterotrimeric type I collagen by coordinating the translation of collagen mRNAs.
Cai
Le
L
Department of Biomedical Sciences, College of Medicine, Florida State University, 1115 West Call Street, Tallahassee, FL 32306, USA.
Fritz
Dillon
D
Stefanovic
Lela
L
Stefanovic
Branko
B
D000818:Animals; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009218:Myosins / Q000378:metabolism*; D011132:Polyribosomes / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism
D024042:Collagen Type I; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D009218:Myosins