UNC-45a promotes myosin folding and stress fiber assembly

Lehtimäki, Jaakko; Fenix, Aidan M.; Kotila, Tommi; Balistreri, Giuseppe; Paavolainen, Lassi; Varjosalo, Markku; Burnette, Dylan T.; Lappalainen, Pekka

doi:10.1083/jcb.201703107

Cited by 41 publications

(48 citation statements)

References 87 publications

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“…Furthermore, our data reveal that myosin-18B is important for migration of osteosarcoma cells, especially in a 3D matrix, but whether this is due to defects in the formation of thick actomyosin bundles, or due to some other cellular functions of myosin-18B, remains to be elucidated. The effects of myosin-18B depletion on cell migration are also somewhat contradictory to earlier studies, where depletion of NMII enhanced cell migration [35–37]. It is possible that the migration defects of myosin-18B knockout cells arise from their decreased polarity (as measured by circularity index; Figure S3G).…”

Section: Disscussioncontrasting

confidence: 62%

Myosin-18B Promotes the Assembly of Myosin II Stacks for Maturation of Contractile Actomyosin Bundles

et al. 2019

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SUMMARY Cell adhesion, morphogenesis, mechanosensing, and muscle contraction rely on contractile actomyosin bundles, where the force is produced through sliding of bipolar myosin II filaments along actin filaments. The assembly of contractile actomyosin bundles involves registered alignment of myosin II filaments and their subsequent fusion into large stacks. However, mechanisms underlying the assembly of myosin II stacks, and their physiological functions have remained elusive. Here we identified myosin-18B, an unconventional myosin, as a stable component of contractile stress fibers. Myosin-18B co-localized with myosin II motor domains in stress fibers, and was enriched at the ends of myosin II stacks. Importantly, myosin-18B deletion resulted in drastic defects in the concatenation and persistent association of myosin II filaments with each other, and thus led to severely impaired assembly of myosin II stacks. Consequently, lack of myosin-18B resulted in defective maturation of actomyosin bundles from their precursors in osteosarcoma cells. Moreover, myosin-18B knockout cells displayed abnormal morphogenesis, migration, and ability to exert forces to the environment. These results reveal a critical role for myosin-18B in myosin II stack assembly, and provide evidence that myosin II stacks are important for a variety of vital processes in cells.

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Section: Disscussioncontrasting

confidence: 62%

Myosin-18B Promotes the Assembly of Myosin II Stacks for Maturation of Contractile Actomyosin Bundles

et al. 2019

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“…NMII-F stack, which is an arrayed structure consisting of multiple bipolar NMII filaments, was previously detected in lamella of fibroblasts by electron microscopy and suggested to be important for formation of actin filament bundles in this region [29]. Super-resolution imaging modalities, such as structured illumination microscopy (SIM), revealed the dynamic organization of NMII-F stacks, which are generated at the distal region of lamella and expanded during their inward flow [30][31][32][33]. NMII-F stacks were also previously observed in the cleavage furrow by SIM and suggested to contribute to proper orientation of actin filaments and generation of a larger contractile force in the contractile ring [30,33].…”

Section: An Appropriate Level Of Nmiia and Nmiib Is Important For Normentioning

confidence: 99%

“…Super-resolution imaging modalities, such as structured illumination microscopy (SIM), revealed the dynamic organization of NMII-F stacks, which are generated at the distal region of lamella and expanded during their inward flow [30][31][32][33]. NMII-F stacks were also previously observed in the cleavage furrow by SIM and suggested to contribute to proper orientation of actin filaments and generation of a larger contractile force in the contractile ring [30,33]. Treatment with a low concentration of blebbistatin, an inhibitor of NMII ATPase activity, shortens NMII-F stacks and decelerates furrow ingression [30], suggesting that proper organization of NMII-F stacks correlates with proper progression of furrow ingression.…”

Section: An Appropriate Level Of Nmiia and Nmiib Is Important For Normentioning

confidence: 99%

Differential contributions of nonmuscle myosin IIA and IIB to cytokinesis in human immortalized fibroblasts

Yamamoto

Otomo

Nemoto

et al. 2019

Experimental Cell Research

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Nonmuscle myosin II (NMII) plays an important role in cytokinesis by constricting a contractile ring. However, it is unknown how NMII isoforms contribute to cytokinesis in mammalian cells. Here, we investigated the roles of the two major NMII isoforms, NMIIA and NMIIB, in cytokinesis using a WI-38 VA13 cell line (human immortalized fibroblast). In this cell line, NMIIB tended to localize to the contractile ring more than NMIIA. The expression level of NMIIA affected the localization of NMIIB and vice versa. Most NMIIB accumulated at the cleavage furrow in NMIIA-knockout (KO) cells, and most NMIIA was displaced from this location in exogenous NMIIB-expressing cells, indicating that NMIIB preferentially localizes to the contractile ring. Specific KO of each isoform elicited opposite effects. The rate of furrow ingression was decreased and increased in NMIIA-KO and NMIIB-KO cells, respectively. Meanwhile, the length of NMII-filament stacks in the contractile ring was increased and decreased in NMIIA-KO and NMIIB-KO cells, respectively. Moreover, NMIIA helped to maintain cortical stiffness during cytokinesis. These findings suggest that appropriate level of NMIIA and NMIIB in the contractile ring is important for proper cytokinesis in specific cell types. In addition, two-photon excitation spinning-disk confocal microscopy enabled us to image constriction of the contractile ring in live cells in a three-dimensional manner.

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“…In other cell types, nonmuscle myosin II (NM-II) isoforms also assemble into contractile actomyosin structures, such as the stress fibers that control cell adhesion, migration, and morphology. In this issue, reveal that nonmuscle cells incorporate myosin into stress fibers via a mechanism similar to the one muscle cells use to assemble myofibrils (1). …”

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confidence: 99%

“…The fact that many cells seem to be perfectly fine expressing low levels of UNC-45a could explain why knocking down the protein by RNAi has little effect. Lehtimäki et al therefore used CRISPR/Cas9 to generate UNC-45a knockout U2OS cells (1). …”

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confidence: 99%

UNC-45a helps cells manage their stress levels

Short¹

2017

Journal of Cell Biology

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UNC-45a promotes myosin folding and stress fiber assembly

Abstract: How nonmuscle myosin II is recruited to contractile actomyosin bundles or stress fibers and assembled into functional bipolar filaments is unclear. Lehtimäki et al. show that UNC-45a functions as a myosin chaperone that contributes to the assembly of functional stress fibers.

Cited by 41 publications

References 87 publications

Myosin-18B Promotes the Assembly of Myosin II Stacks for Maturation of Contractile Actomyosin Bundles

Myosin-18B Promotes the Assembly of Myosin II Stacks for Maturation of Contractile Actomyosin Bundles

Differential contributions of nonmuscle myosin IIA and IIB to cytokinesis in human immortalized fibroblasts

UNC-45a helps cells manage their stress levels

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