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Cited by 47Cellular Mechanics and InteractionsHeat shock proteins researchMicrotubule and mitosis dynamics

UNC-45a promotes myosin folding and stress fiber assembly

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Lehtimäki, Jaakko I., Fenix, Aidan M., Kotila, Tommi M., Balistreri, Giuseppe, Paavolainen, Lassi, Varjosalo, Markku, Burnette, Dylan T., Lappalainen, Pekka·2017·Journal of Cell Biology
DOI 10.1083/jcb.201703107PMC PMC5716280
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Abstract

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.

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Authors
Lehtimäki, J. I., Fenix, A. M., Kotila, T. M., Balistreri, G., Paavolainen, L., Varjosalo, M., Burnette, D. T., & Lappalainen, P.
Affiliations
  • University of Helsinki (FI)
  • Vanderbilt University (US)
Corresponding author
Lappalainen, Pekka
ORCID
Venue
Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2017-10-20
Volume
216
Issue
12
Pages
4053-4072
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.201703107
PMC
PMC5716280
OpenAlex
W2766092740
Cited by
47
References
2
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2.77
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journal article
Language
en
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  • The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • Työväentutkimus Vuosikirja (submittedVersion)
Funders
  • Sigrid Jusélius Foundation
  • Jane and Aatos Erkko Foundation
  • American Heart Association (17SDG33460353, 16PRE29100014)
  • National Heart, Lung, and Blood Institute (1F31HL136081-01)
  • Integrative Life Science
  • National Institute of General Medical Sciences (R35 GM125028-01)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Keywords
non-muscle myosin II, myosin chaperone, myosin 1c, tetratricopeptide repeat domain, cell morphogenesis, cell polarity, cell migration
MeSH terms
Tetratricopeptide Repeat, Actomyosin, Cell Adhesion, Cell Movement, Humans, Osteoblasts, Gene Expression, Cell Polarity, Protein Folding, Protein Isoforms, Stress Fibers, Myosin Type II, Cell Line, Tumor, Proteasome Endopeptidase Complex, Intracellular Signaling Peptides and Proteins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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