Myosin IIIa boosts elongation of stereocilia by transporting espin 1 to the plus ends of actin filaments

Salles, Felipe T.; Merritt, Raymond C.; Manor, Uri; Dougherty, Gerard W.; Sousa, Aurea D.; Moore, Judy E.; Yengo, Christopher M.; Dosé, Andréa C.; Kachar, Bechara

doi:10.1038/ncb1851

Cited by 138 publications

(269 citation statements)

References 32 publications

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“…As neither Myo3a −/− mice nor Myo3b −/− mice exhibit early hearing impairment, this demonstrates that myosins IIIa and IIIb are able to compensate for the loss of each other in the developing cochlea. A role for myosin IIIa in the maintenance of mature stereocilia has been suggested based on the implication of this protein in the DFNB30 late-onset form of deafness (Walsh et al, 2002), its localization at the tips of stereocilia (Schneider et al, 2006), and in vitro evidence of the elongation of stereocilia when myosin IIIa is overexpressed with espin-1 in hair cells at postnatal stages (Salles et al, 2009). Remarkably, the absence of hearing loss in Myo3a-cKO Myo3b −/− mice pinpoints the compensatory mechanisms between myosins IIIa and IIIb as being critical during the period of hair bundle formation, but contrary to earlier suggestions, not at mature stages (Walsh et al, 2002;Schneider et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…The myosin IIIa binding partners espin-1 and MORN4 are targeted to the tips of cochlear stereocilia in Myo3a −/− Myo3b −/− mice Espins, a class of actin-bundling proteins critical for the formation of stereocilia and other actin-filled protrusions (Loomis et al, 2003), include espin-1, which has been proposed to be targeted to the stereocilia tips by myosin IIIa (Salles et al, 2009). We thus investigated whether this protein is present in the cochlear hair bundles of Myo3a −/− Myo3b −/− mice.…”

Section: Cochlear Hair Cells Of Myo3a −/− Myo3b −/− Mice Display Robumentioning

confidence: 99%

“…For myosin IIIa, we used the amino acid sequence reported in a previous study (Schneider et al, 2006). For myosin IIIb, we used the sequence SPE DTMYY NQLNG TLEYQ GSQRK PRKLG QIKVL DGEDQ YYKCL SPGAC APE ET HSVHP FFFSS SPRED PFAQH (Agro-Bio), and for espin-1, we used the sequence LDA LPVHH AARSG KLHCLR (Proteogenix; Salles et al, 2009). We checked that our anti-myosin IIIa and anti-myosin IIIb antibodies were specific by immunofluorescence experiments in which Myo3a −/− and Myo3b −/− mice were used as negative controls (Fig.…”

Section: Antibodies and Immunostaining Of Whole-mount Cochleasmentioning

confidence: 99%

“…When overexpressed in HeLa cells (Les Erickson et al, 2003) and in hair cells of cultured auditory organs (Schneider et al, 2006), a GFP-myosin IIIa fusion protein localizes at the tips of the filopodia and stereocilia. Furthermore, when myosin IIIa and the F-actin bundling and ankyrin repeat-containing protein espin-1 are both overexpressed in hair cells, they concentrate at the tips of the stereocilia, and the latter elongate (Salles et al, 2009). Myosin IIIa has been shown to transport espin-1 to the tips of filopodia in COS-7 cells, through the binding of its conserved tail homology domain, 3THDI, to the ankyrin repeat domain of espin-1, thereby providing a plausible mechanism by which myosin IIIa could promote F-actin polymerization in filopodia and stereocilia (Salles et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Class III myosins shape the auditory hair bundles by limiting microvilli and stereocilia growth

Lelli¹,

Michel²,

Monvel³

et al. 2016

J Gen Physiol

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Section: Discussionmentioning

confidence: 99%

Section: Cochlear Hair Cells Of Myo3a −/− Myo3b −/− Mice Display Robumentioning

confidence: 99%

Section: Antibodies and Immunostaining Of Whole-mount Cochleasmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Class III myosins shape the auditory hair bundles by limiting microvilli and stereocilia growth

Lelli¹,

Michel²,

Monvel³

et al. 2016

J Gen Physiol

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“…M olecular motor transport in a living cell is one of the most fascinating processes in cellular biophysics. Molecular motors play crucial roles in many elongated organelles, such as neuronal axons (1), flagella (2), filopodia (3), stereocilia (4,5), and microvilli (4). A naive view of cellular motor transport is that of motor molecules orderly following each other on the substrate and carrying cargo, which they unload at a destination point.…”

mentioning

confidence: 99%

Theory of active transport in filopodia and stereocilia

Zhuravlev

Lan

Minakova

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The biological processes in elongated organelles of living cells are often regulated by molecular motor transport. We determined spatial distributions of motors in such organelles, corresponding to a basic scenario when motors only walk along the substrate, bind, unbind, and diffuse. We developed a mean-field model, which quantitatively reproduces elaborate stochastic simulation results as well as provides a physical interpretation of experimentally observed distributions of Myosin IIIa in stereocilia and filopodia. The mean-field model showed that the jamming of the walking motors is conspicuous, and therefore damps the active motor flux. However, when the motor distributions are coupled to the delivery of actin monomers toward the tip, even the concentration bump of G actin that they create before they jam is enough to speed up the diffusion to allow for severalfold longer filopodia. We found that the concentration profile of G actin along the filopodium is rather nontrivial, containing a narrow minimum near the base followed by a broad maximum. For efficient enough actin transport, this nonmonotonous shape is expected to occur under a broad set of conditions. We also find that the stationary motor distribution is universal for the given set of model parameters regardless of the organelle length, which follows from the form of the kinetic equations and the boundary conditions. M olecular motor transport in a living cell is one of the most fascinating processes in cellular biophysics. Molecular motors play crucial roles in many elongated organelles, such as neuronal axons (1), flagella (2), filopodia (3), stereocilia (4, 5), and microvilli (4). A naive view of cellular motor transport is that of motor molecules orderly following each other on the substrate and carrying cargo, which they unload at a destination point. However, in reality, motors not only walk, but also diffuse around the cell, randomly binding and unbinding to their substrate filaments and/or cargo. To a large extent these processes are governed by molecular noise. To understand how the motors perform their functions-be it cargo delivery to the growing end of an organelle or creating stresses in a flagellum, or even in artificial systems (6, 7)-it is necessary to know their spatial distribution in these systems.The spatial distribution of the motors could influence the delivery of building material toward the growing end of a dynamic elongated organelle, such as a filopodium or a stereocilium. In the absence of motors, the length of such organelle is expected to be limited by the slow diffusional delivery of the material to the tip (8). Furthermore, prior computational modeling of simple, conveyor-belt-like transport of monomeric species by molecular motors indicated that specially designed cooperative mechanisms are needed to achieve any appreciable active transport flux (9). Two main reasons for the transport inefficiency are sequestration of cargo by motors and diminution of motor speeds due to clogging of the filamentous bundle by walking mo...

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Changes in plasma membrane structure and electromotile properties in prestin deficient outer hair cells

Song

Sato

et al. 2009

Cytoskeleton

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Cochlear outer hair cells (OHCs) rapidly change their length and stiffness when their membrane potential is altered. Prestin, the motor protein for this electromotility, is present along the OHC lateral plasma membrane where there is a high density of intra-membrane protein particles (IMPs). However, it is not known to what extent prestin contributes to this unusual dense population of proteins and overall organization of the membrane to generate the unique electromechanical response of OHCs. We investigated the relationship of prestin with the IMPs, the underlying cortical cytoskeletal lattice, and electromotility in prestin-deficient mice. Using freeze-fracture, we observed a reduction in density and size of the IMPs that correlates with the reduction and absence of prestin in the heterozygous and homozygous mice, respectively. We also observed a reduction or absence of electromotility-related charge density, axial stiffness, and piezoelectric properties of the OHC. A comparison of the charge density with the number of IMPs suggests that prestin forms tetramers in the wild type but is likely to form lower number oligomers in the prestin-deficient OHCs from the heterozygous mice. Interestingly, the characteristic actin-based cortical cytoskeletal lattice that underlies the membrane is absent in the prestin-null OHCs, suggesting that prestin is also required for recruiting or maintaining the cortical cytoskeletal lattice. These results suggest that the majority of the IMPs are indeed prestin and that electrically evoked length and stiffness changes are interrelated and dependent on both prestin and on the cortical actin cytoskeletal lattice of the OHC lateral membrane.

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Myosin IIIa boosts elongation of stereocilia by transporting espin 1 to the plus ends of actin filaments

Cited by 138 publications

References 32 publications

Class III myosins shape the auditory hair bundles by limiting microvilli and stereocilia growth

Class III myosins shape the auditory hair bundles by limiting microvilli and stereocilia growth

Theory of active transport in filopodia and stereocilia

Changes in plasma membrane structure and electromotile properties in prestin deficient outer hair cells

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