UNC-45a promotes myosin folding and stress fiber assembly.

Lehtimäki JI, Fenix AM, Kotila TM, Balistreri G, Paavolainen L, Varjosalo M, Burnette DT, Lappalainen P
J Cell Biol. 2017 216 (12): 4053-4072

PMID: 29055011 · PMCID: PMC5716280 · DOI:10.1083/jcb.201703107

Contractile actomyosin bundles, stress fibers, are crucial for adhesion, morphogenesis, and mechanosensing in nonmuscle cells. However, the mechanisms by which nonmuscle myosin II (NM-II) is recruited to those structures and assembled into functional bipolar filaments have remained elusive. We report that UNC-45a is a dynamic component of actin stress fibers and functions as a myosin chaperone in vivo. UNC-45a knockout cells display severe defects in stress fiber assembly and consequent abnormalities in cell morphogenesis, polarity, and migration. Experiments combining structured-illumination microscopy, gradient centrifugation, and proteasome inhibition approaches revealed that a large fraction of NM-II and myosin-1c molecules fail to fold in the absence of UNC-45a. The remaining properly folded NM-II molecules display defects in forming functional bipolar filaments. The C-terminal UNC-45/Cro1/She4p domain of UNC-45a is critical for NM-II folding, whereas the N-terminal tetratricopeptide repeat domain contributes to the assembly of functional stress fibers. Thus, UNC-45a promotes generation of contractile actomyosin bundles through synchronized NM-II folding and filament-assembly activities.

© 2017 Lehtimäki et al.

MeSH Terms (15)

Actomyosin Cell Adhesion Cell Line, Tumor Cell Movement Cell Polarity Gene Expression Humans Intracellular Signaling Peptides and Proteins Myosin Type II Osteoblasts Proteasome Endopeptidase Complex Protein Folding Protein Isoforms Stress Fibers Tetratricopeptide Repeat

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