An interaction between myosin-10 and the cell cycle regulator Wee1 links spindle dynamics to mitotic progression in epithelia

Sandquist, Joshua C.; Larson, Matthew E.; Woolner, Sarah; Ding, Zhongli

doi:10.1083/jcb.201708072

Cited by 14 publications

(24 citation statements)

References 51 publications

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“…The roles, if any, played by the fingers are even more mysterious. However, because it was previously proposed that communication between the spindle poles and cortex is involved in the metaphase–anaphase transition in these cells (Larson and Bement, 2017; Sandquist, Larson et al , 2018), we are attracted to the possibility that the F-actin fingers may represent a conduit for exchange of cell cycle control proteins between the spindle and the cortex.…”

Section: Resultsmentioning

confidence: 99%

Spindle–F-actin interactions in mitotic spindles in an intact vertebrate epithelium

Kita

Swider

Erofeev

et al. 2019

MBoC

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Mitotic spindles are well known to be assembled from and dependent on microtubules. In contrast, whether actin filaments (F-actin) are required for or are even present in mitotic spindles has long been controversial. Here we have developed improved methods for simultaneously preserving F-actin and microtubules in fixed samples and exploited them to demonstrate that F-actin is indeed associated with mitotic spindles in intact Xenopus laevis embryonic epithelia. We also find that there is an “F-actin cycle,” in which the distribution and organization of spindle F-actin changes over the course of the cell cycle. Live imaging using a probe for F-actin reveals that at least two pools of F-actin are associated with mitotic spindles: a relatively stable internal network of cables that moves in concert with and appears to be linked to spindles, and F-actin “fingers” that rapidly extend from the cell cortex toward the spindle and make transient contact with the spindle poles. We conclude that there is a robust endoplasmic F-actin network in normal vertebrate epithelial cells and that this network is also a component of mitotic spindles. More broadly, we conclude that there is far more internal F-actin in epithelial cells than is commonly believed.

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Section: Resultsmentioning

confidence: 99%

Spindle–F-actin interactions in mitotic spindles in an intact vertebrate epithelium

Kita

Swider

Erofeev

et al. 2019

MBoC

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“…As MYO10 is involved in spindle dynamics ( Kwon et al., 2015 ; Woolner et al., 2008 ; Sandquist et al., 2018 ), we stained MYO10-intact and -deleted cells for pericentrin and γ-tubulin to visualize the centrosomes. In PTEN(−/−) cells ( Figure 2 C), pericentrin and γ-tubulin staining define a punctate, perinuclear structure, consistent with the appearance of centrosomes in interphase.…”

Section: Resultsmentioning

confidence: 99%

“…It is upregulated in lung, prostate, and breast carcinomas; its level of expression in melanoma correlates with metastatic capacity; and its deletion reduces metastases and prolongs survival in a mouse model of melanoma ( Bidkhori et al., 2013 ; Cao et al., 2014 ; Arjonen et al., 2014 ; Sun et al., 2015 ; Makowska et al., 2015 ; Tokuo et al., 2018 ). In addition, MYO10 plays a role in mitosis by localizing a variety of mitotic and spindle regulators, including microtubules, TPX2, and Wee1, through the MyTH4/FERM domain in its C-terminal tail ( Kwon et al., 2015 ; Woolner et al., 2008 ; Sandquist et al., 2018 ). MYO10 also binds several signaling proteins, including β integrins and PKCι ( Zhang et al., 2004 ; Linch et al., 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Myosin 10 Regulates Invasion, Mitosis, and Metabolic Signaling in Glioblastoma

et al. 2020

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Summary Invasion and proliferation are defining phenotypes of cancer, and in glioblastoma blocking one stimulates the other, implying that effective therapy must inhibit both, ideally through a single target that is also dispensable for normal tissue function. The molecular motor myosin 10 meets these criteria. Myosin 10 knockout mice can survive to adulthood, implying that normal cells can compensate for its loss; its deletion impairs invasion, slows proliferation, and prolongs survival in murine models of glioblastoma. Myosin 10 deletion also enhances tumor dependency on the DNA damage and the metabolic stress responses and induces synthetic lethality when combined with inhibitors of these processes. Our results thus demonstrate that targeting myosin 10 is active against glioblastoma by itself, synergizes with other clinically available therapeutics, may have acceptable side effects in normal tissues, and has potential as a heretofore unexplored therapeutic approach for this disease.

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“…It is unclear if, or how, cells delay mitotic progression and cytokinesis until their spindles are in the right place but suggest that an interaction between the motor protein myosin-10 and the cell cycle regulator Wee1 could help coordinate spindle positioning and mitotic exit (1). …”

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confidence: 99%

“…Now, Sandquist and colleagues, including Matthew Larson and Bill Bement from the University of Wisconsin-Madison,found that myosin-10’s MyTH4 domain binds to Wee1 (1). The two proteins colocalized near the poles of Xenopus mitotic spindles.…”

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confidence: 99%