Protrusion growth driven by myosin-generated force

Fitz, Gillian N.; Weck, Meredith L.; Bodnya, Caroline; Perkins, Olivia L.; Tyska, Matthew J.

doi:10.1016/j.devcel.2022.12.001

Cited by 14 publications

(33 citation statements)

References 89 publications

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“…Two other mechanisms may be utilized by MYO10 and MYO3A to move in F-actin protrusions. Anchoring to the plasma membrane can be used by MYO10 to form F-actin protrusions at the cell edge and then move toward the tip in the protrusion ( Fitz et al, 2023 ). Binding to F-actin is necessary for MYO3A to move in a stereocilium or a filopodium ( Salles et al, 2009 ; Raval et al, 2016 ).…”

Section: Myosins and Hearing Lossmentioning

confidence: 99%

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Pathophysiology of human hearing loss associated with variants in myosins

Miyoshi,

Belyantseva,

Sajeevadathan

et al. 2024

Front. Physiol.

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Deleterious variants of more than one hundred genes are associated with hearing loss including MYO3A, MYO6, MYO7A and MYO15A and two conventional myosins MYH9 and MYH14. Variants of MYO7A also manifest as Usher syndrome associated with dysfunction of the retina and vestibule as well as hearing loss. While the functions of MYH9 and MYH14 in the inner ear are debated, MYO3A, MYO6, MYO7A and MYO15A are expressed in inner ear hair cells along with class-I myosin MYO1C and are essential for developing and maintaining functional stereocilia on the apical surface of hair cells. Stereocilia are large, cylindrical, actin-rich protrusions functioning as biological mechanosensors to detect sound, acceleration and posture. The rigidity of stereocilia is sustained by highly crosslinked unidirectionally-oriented F-actin, which also provides a scaffold for various proteins including unconventional myosins and their cargo. Typical myosin molecules consist of an ATPase head motor domain to transmit forces to F-actin, a neck containing IQ-motifs that bind regulatory light chains and a tail region with motifs recognizing partners. Instead of long coiled-coil domains characterizing conventional myosins, the tails of unconventional myosins have various motifs to anchor or transport proteins and phospholipids along the F-actin core of a stereocilium. For these myosins, decades of studies have elucidated their biochemical properties, interacting partners in hair cells and variants associated with hearing loss. However, less is known about how myosins traffic in a stereocilium using their motor function, and how each variant correlates with a clinical condition including the severity and onset of hearing loss, mode of inheritance and presence of symptoms other than hearing loss. Here, we cover the domain structures and functions of myosins associated with hearing loss together with advances, open questions about trafficking of myosins in stereocilia and correlations between hundreds of variants in myosins annotated in ClinVar and the corresponding deafness phenotypes.

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Section: Myosins and Hearing Lossmentioning

confidence: 99%

“…Interestingly, movements of human MYO7A are slower than Drosophila myosin VIIa (crinkled), 72 ± 20 nm/s ( Sato et al, 2017 ). The slow movements of MYO7A might prevent this motor protein from behaving like MYO10, which makes cellular protrusions when anchored to the plasma membrane ( Fitz et al, 2023 ).…”

Section: Myosins and Hearing Lossmentioning

confidence: 99%

Pathophysiology of human hearing loss associated with variants in myosins

Miyoshi,

Belyantseva,

Sajeevadathan

et al. 2024

Front. Physiol.

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“…IL2Rα and MYO7A-HMM were conditionally heterodimerized by fusing FKBP and FKBP-Rapamycin binding protein (FRB) to the C-terminus of each protein and supplementing the culture medium with a Rapamycin analog, AP21987 68 . Bovine MYO10 lacking the entire tail and the coiled-coil domain for anti-parallel dimerization (MYO10-MD) in the neck 66 was used as a positive control. Fluorescence confocal microscopy shows that HaloTag-MYO7A-HMM-FRB is successfully anchored to the plasma membrane after AP21987 treatment (Fig.…”

Section: Distinct Behavior Of Myo7a and Myo10 Anchored To The Plasma ...mentioning

confidence: 99%

Live-cell single-molecule fluorescence microscopy for protruding organelles reveals regulatory mechanisms of MYO7A-driven cargo transport in stereocilia of inner ear hair cells

Miyoshi,

Vishwasrao,

Belyantseva

et al. 2024

Preprint

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Stereocilia are unidirectional F-actin-based cylindrical protrusions on the apical surface of inner ear hair cells and function as biological mechanosensors of sound and acceleration. Development of functional stereocilia requires motor activities of unconventional myosins to transport proteins necessary for elongating the F-actin cores and to assemble the mechanoelectrical transduction (MET) channel complex. However, how each myosin localizes in stereocilia using the energy from ATP hydrolysis is only partially understood. In this study, we develop a methodology for live-cell single-molecule fluorescence microscopy of organelles protruding from the apical surface using a dual-view light-sheet microscope, diSPIM. We demonstrate that MYO7A, a component of the MET machinery, traffics as a dimer in stereocilia. Movements of MYO7A are restricted when scaffolded by the plasma membrane and F-actin as mediated by MYO7A’s interacting partners. Here, we discuss the technical details of our methodology and its future applications including analyses of cargo transportation in various organelles.

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“…Oocyte maturation, fertilization, and early embryonic development are accompanied by cell surface remodeling [20,21], cell division [22,23], cell polarization [24,25], intercellular junction formation, cell adhesion [26,27] cell migration [28,29] and other activities [30][31][32]. Studies have shown that ERM proteins are expressed in oocytes and early embryos.…”

mentioning

confidence: 99%

Ezrin Thr567 phosphorylation participates in mouse oocyte maturation, fertilization, and early embryonic development

Xie,

Xia,

Zhang

et al. 2024

Preprint

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Background Ezrin is a membrane-cytoskeleton linker, involved in cell polarization, cell migration, cell division, signal transduction and some other cellular activities that play an important role in oocyte maturation, fertilization and early embryonic development. The phosphorylation of Thr567 is an important way to activate ezrin, it has been proved that p-ezrin Thr567 is expressed in oocytes and pre-implantation embryos in mouse. However, little is known about the impact of inhibiting ezrin Thr567 phosphorylation on oocyte maturation, fertilization and early embryonic development. Methods NSC668394 is a small molecule that specifically inhibits the phosphorylation of ezrin Thr567. Here, we investigated the effects of inhibiting ezrin Thr567 phosphorylation with NSC668394 on the mouse oocyte maturation, fertilization, and early embryo development. Conclusion The results show that adding NSC668394 to the in vitro culture medium significantly lowed mouse embryos development competence after 8-cell stage (P < 0.05). Further experiments revealed that inhibiting ezrin Thr567 phosphorylation during in vitro maturation or in vitro fertilization not only decreased the maturation rate and fertilization rate of mouse oocytes, but also reduced early embryos development competence after 8-cell stage. Microinjection of mRNA encoding ezrin T567D mutant partially rescued the developmental defects of mouse oocytes, fertilization, and early embryonic development caused by NSC668394. These results indicate that ezrin Thr567 phosphorylation plays an important role in mouse oocyte maturation, fertilization and early embryo development.

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Protrusion growth driven by myosin-generated force

Cited by 14 publications

References 89 publications

Pathophysiology of human hearing loss associated with variants in myosins

Pathophysiology of human hearing loss associated with variants in myosins

Live-cell single-molecule fluorescence microscopy for protruding organelles reveals regulatory mechanisms of MYO7A-driven cargo transport in stereocilia of inner ear hair cells

Ezrin Thr567 phosphorylation participates in mouse oocyte maturation, fertilization, and early embryonic development

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