The Experts below are selected from a list of 465 Experts worldwide ranked by ideXlab platform
Jocelyn F. Krey - One of the best experts on this subject based on the ideXlab platform.
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A cryo-tomography-based volumetric model of the actin core of mouse vestibular hair cell stereocilia lacking plastin 1.
Journal of structural biology, 2020Co-Authors: Junha Song, Roma Patterson, Jocelyn F. Krey, Samantha Hao, Linshanshan Wang, Salim Sazzed, Julio A. Kovacs, Zoltan Metlagel, Willy WriggersAbstract:Abstract Electron cryo-tomography allows for high-resolution imaging of stereocilia in their native state. Because their actin filaments have a higher degree of order, we imaged stereocilia from mice lacking the actin crosslinker plastin 1 (PLS1). We found that while stereocilia actin filaments run 13 nm apart in parallel for long distances, there were gaps of significant size that were stochastically distributed throughout the actin core. Actin crosslinkers were distributed through the Stereocilium, but did not occupy all possible binding sites. At stereocilia tips, protein density extended beyond actin filaments, especially on the side of the tip where a tip link is expected to anchor. Along the shaft, repeating density was observed that corresponds to actin-to-membrane connectors. In the taper region, most actin filaments terminated near the plasma membrane. The remaining filaments twisted together to make a tighter bundle than was present in the shaft region; the spacing between them decreased from 13 nm to 9 nm, and the apparent filament diameter decreased from 6.4 to 4.8 nm. Our models illustrate detailed features of distinct structural domains that are present within the Stereocilium.
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A cryo-tomography-based volumetric model of the actin core of mouse vestibular hair cell stereocilia lacking plastin 1
2019Co-Authors: Junha Song, Roma Patterson, Jocelyn F. Krey, Samantha Hao, Linshanshan Wang, Salim Sazzed, Julio A. Kovacs, Willy WriggersAbstract:Electron cryo-tomography allows for high-resolution imaging of stereocilia in their native state. Because their actin filaments have a higher degree of order, we imaged stereocilia from mice lacking the actin crosslinker plastin 1 (PLS1). We found that while stereocilia actin filaments run in parallel for long distances, 13 nm apart, there were gaps of significant size that were stochastically distributed throughout the actin core. Actin crosslinkers were distributed through the Stereocilium, but did not occupy all possible binding sites. At stereocilia tips, protein density extended beyond actin filaments, especially on the side of the tip where a tip link should anchor. Along the shaft, repeating density was observed that corresponds to actin-to-membrane connectors. In the taper region, most actin filaments terminated near the plasma membrane. The remaining filaments twisted together to make a tighter bundle than was present in the shaft region; the spacing between them decreased from 13 nm to 9 nm. Our models illustrate detailed features of distinct structural domains that are present within the Stereocilium.
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Heterodimeric capping protein is required for stereocilia length and width regulation.
The Journal of cell biology, 2017Co-Authors: Matthew R. Avenarius, David P. Corey, Jocelyn F. Krey, Rachel A. Dumont, Clive P Morgan, Connor B. Benson, Sarath Vijayakumar, Christopher L. Cunningham, Deborah I. Scheffer, Ulrich MüllerAbstract:Control of the dimensions of actin-rich processes like filopodia, lamellipodia, microvilli, and stereocilia requires the coordinated activity of many proteins. Each of these actin structures relies on heterodimeric capping protein (CAPZ), which blocks actin polymerization at barbed ends. Because dimension control of the inner ear’s stereocilia is particularly precise, we studied the CAPZB subunit in hair cells. CAPZB, present at ∼100 copies per Stereocilium, concentrated at stereocilia tips as hair cell development progressed, similar to the CAPZB-interacting protein TWF2. We deleted Capzb specifically in hair cells using Atoh1-Cre, which eliminated auditory and vestibular function. Capzb-null stereocilia initially developed normally but later shortened and disappeared; surprisingly, stereocilia width decreased concomitantly with length. CAPZB2 expressed by in utero electroporation prevented normal elongation of vestibular stereocilia and irregularly widened them. Together, these results suggest that capping protein participates in stereocilia widening by preventing newly elongating actin filaments from depolymerizing.
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Molecular architecture of the chick vestibular hair bundle
Nature Neuroscience, 2013Co-Authors: Jung-bum Shin, Kateri J. Spinelli, Jocelyn F. Krey, Zoltan Metlagel, Ahmed Hassan, James M. Pagana, Nicholas E. Sherman, Erin D. Jeffery, Andrew N Tauscher, Hongyu ZhaoAbstract:In this Resource study, the authors used high-resolution mass spectrometry to elucidate the precise proteomic complement of the inner ear hair bundle. Many of the proteins that are enriched in the hair bundles are encoded by known deafness-associated genes. Hair bundles of the inner ear have a specialized structure and protein composition that underlies their sensitivity to mechanical stimulation. Using mass spectrometry, we identified and quantified >1,100 proteins, present from a few to 400,000 copies per Stereocilium, from purified chick bundles; 336 of these were significantly enriched in bundles. Bundle proteins that we detected have been shown to regulate cytoskeleton structure and dynamics, energy metabolism, phospholipid synthesis and cell signaling. Three-dimensional imaging using electron tomography allowed us to count the number of actin-actin cross-linkers and actin-membrane connectors; these values compared well to those obtained from mass spectrometry. Network analysis revealed several hub proteins, including RDX (radixin) and SLC9A3R2 (NHERF2), which interact with many bundle proteins and may perform functions essential for bundle structure and function. The quantitative mass spectrometry of bundle proteins reported here establishes a framework for future characterization of dynamic processes that shape bundle structure and function.
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Molecular architecture of the chick vestibular hair bundle.Nat
2013Co-Authors: Jung-bum Shin, Kateri J. Spinelli, Jocelyn F. Krey, Zoltan Metlagel, Ahmed Hassan, Andrew N, James M. Pagana, Nicholas E. Sherman, Erin D. Jeffery, Hongyu ZhaoAbstract:Hair bundles of the inner ear have a unique structure and protein composition that underlies their sensitivity to mechanical stimulation. Using mass spectrometry, we identified and quantified>1100 proteins, present from a few to 400,000 copies per Stereocilium, from purified chick bundles; 336 of these were significantly enriched in bundles. Bundle proteins that we detected have been shown to regulate cytoskeleton structure and dynamics, energy metabolism, phospholipid synthesis, and cell signaling. Three-dimensional imaging using electron tomography allowed us to count the number of actin-actin crosslinkers and actin-membrane connectors; these values compared well to those obtained from mass spectrometry. Network analysis revealed several hub proteins, including RDX (radixin) and SLC9A3R2 (NHERF2), which interact with many bundle proteins and may perform functions essential for bundle structure and function. The quantitative mass spectrometry of bundle proteins reported here establishes a framework for future characterization of dynamic processes that shape bundle structure and function
Anders Fridberger - One of the best experts on this subject based on the ideXlab platform.
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Sound-induced length changes in outer hair cell stereocilia
Nature Communications, 2012Co-Authors: Pierre Hakizimana, William E. Brownell, Stefan Jacob, Anders FridbergerAbstract:In the inner ear, sound waves produce movements in hair cell sterocilia, triggering the opening of ion channels. Hakizimana and colleagues show that the resultant currents change the length of sterocilia, and that these length changes alter the efficiency by which sound is converted into electrical signals. Hearing relies on mechanical stimulation of stereocilia bundles on the sensory cells of the inner ear. When sound hits the ear, each Stereocilium pivots about a neck-like taper near their base. More than three decades of research have established that sideways deflection of stereocilia is essential for converting mechanical stimuli into electrical signals. Here we show that mammalian outer hair cell stereocilia not only move sideways but also change length during sound stimulation. Currents that enter stereocilia through mechanically sensitive ion channels control the magnitude of both length changes and bundle deflections in a reciprocal manner: the smaller the length change, the larger is the bundle deflection. Thus, the transduction current is important for maintaining the resting mechanical properties of stereocilia. Hair cell stimulation is most effective when bundles are in a state that ensures minimal length change.
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Sound-induced length changes in outer hair cell stereocilia
Nature communications, 2012Co-Authors: Pierre Hakizimana, William E. Brownell, Stefan Jacob, Anders FridbergerAbstract:Hearing relies on mechanical stimulation of stereocilia bundles on the sensory cells of the inner ear. When sound hits the ear, each Stereocilium pivots about a neck-like taper near their base. More than three decades of research have established that sideways deflection of stereocilia is essential for converting mechanical stimuli into electrical signals. Here we show that mammalian outer hair cell stereocilia not only move sideways but also change length during sound stimulation. Currents that enter stereocilia through mechanically sensitive ion channels control the magnitude of both length changes and bundle deflections in a reciprocal manner: the smaller the length change, the larger is the bundle deflection. Thus, the transduction current is important for maintaining the resting mechanical properties of stereocilia. Hair cell stimulation is most effective when bundles are in a state that ensures minimal length change.
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Sound‐Evoked Length Changes of the Outer Hair Cell Stereocilia Bundle are Modulated by Endocochlear Currents
2011Co-Authors: Pierre Hakizimana, William E. Brownell, Stefan Jacob, Anders FridbergerAbstract:The apical surface of vertebrate inner ear sensory cells is characterized by a bundle of giant microvilli commonly known as stereocilia. Stereocilia bend about a neck‐like thinning near their base and more than three decades of research has established that the direction and magnitude of sideways bundle deflection is the basis of the mechanoelectrical signalling that initiates sound perception. Aside from its ability to bend at the neck, the Stereocilium is usually considered as a stiff inelastic rod. Here we show that the length of OHC stereocilia changes during sound transduction, demonstrating their axial compliance, and that the magnitude of the length change is modulated by currents that mimic in vivo endocochlear currents. A reciprocal relation between length change and bundle deflection is evident: the smaller the length changes, the larger the bundle deflection.
Willy Wriggers - One of the best experts on this subject based on the ideXlab platform.
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A cryo-tomography-based volumetric model of the actin core of mouse vestibular hair cell stereocilia lacking plastin 1.
Journal of structural biology, 2020Co-Authors: Junha Song, Roma Patterson, Jocelyn F. Krey, Samantha Hao, Linshanshan Wang, Salim Sazzed, Julio A. Kovacs, Zoltan Metlagel, Willy WriggersAbstract:Abstract Electron cryo-tomography allows for high-resolution imaging of stereocilia in their native state. Because their actin filaments have a higher degree of order, we imaged stereocilia from mice lacking the actin crosslinker plastin 1 (PLS1). We found that while stereocilia actin filaments run 13 nm apart in parallel for long distances, there were gaps of significant size that were stochastically distributed throughout the actin core. Actin crosslinkers were distributed through the Stereocilium, but did not occupy all possible binding sites. At stereocilia tips, protein density extended beyond actin filaments, especially on the side of the tip where a tip link is expected to anchor. Along the shaft, repeating density was observed that corresponds to actin-to-membrane connectors. In the taper region, most actin filaments terminated near the plasma membrane. The remaining filaments twisted together to make a tighter bundle than was present in the shaft region; the spacing between them decreased from 13 nm to 9 nm, and the apparent filament diameter decreased from 6.4 to 4.8 nm. Our models illustrate detailed features of distinct structural domains that are present within the Stereocilium.
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A cryo-tomography-based volumetric model of the actin core of mouse vestibular hair cell stereocilia lacking plastin 1
2019Co-Authors: Junha Song, Roma Patterson, Jocelyn F. Krey, Samantha Hao, Linshanshan Wang, Salim Sazzed, Julio A. Kovacs, Willy WriggersAbstract:Electron cryo-tomography allows for high-resolution imaging of stereocilia in their native state. Because their actin filaments have a higher degree of order, we imaged stereocilia from mice lacking the actin crosslinker plastin 1 (PLS1). We found that while stereocilia actin filaments run in parallel for long distances, 13 nm apart, there were gaps of significant size that were stochastically distributed throughout the actin core. Actin crosslinkers were distributed through the Stereocilium, but did not occupy all possible binding sites. At stereocilia tips, protein density extended beyond actin filaments, especially on the side of the tip where a tip link should anchor. Along the shaft, repeating density was observed that corresponds to actin-to-membrane connectors. In the taper region, most actin filaments terminated near the plasma membrane. The remaining filaments twisted together to make a tighter bundle than was present in the shaft region; the spacing between them decreased from 13 nm to 9 nm. Our models illustrate detailed features of distinct structural domains that are present within the Stereocilium.
Pierre Hakizimana - One of the best experts on this subject based on the ideXlab platform.
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Sound-induced length changes in outer hair cell stereocilia
Nature Communications, 2012Co-Authors: Pierre Hakizimana, William E. Brownell, Stefan Jacob, Anders FridbergerAbstract:In the inner ear, sound waves produce movements in hair cell sterocilia, triggering the opening of ion channels. Hakizimana and colleagues show that the resultant currents change the length of sterocilia, and that these length changes alter the efficiency by which sound is converted into electrical signals. Hearing relies on mechanical stimulation of stereocilia bundles on the sensory cells of the inner ear. When sound hits the ear, each Stereocilium pivots about a neck-like taper near their base. More than three decades of research have established that sideways deflection of stereocilia is essential for converting mechanical stimuli into electrical signals. Here we show that mammalian outer hair cell stereocilia not only move sideways but also change length during sound stimulation. Currents that enter stereocilia through mechanically sensitive ion channels control the magnitude of both length changes and bundle deflections in a reciprocal manner: the smaller the length change, the larger is the bundle deflection. Thus, the transduction current is important for maintaining the resting mechanical properties of stereocilia. Hair cell stimulation is most effective when bundles are in a state that ensures minimal length change.
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Sound-induced length changes in outer hair cell stereocilia
Nature communications, 2012Co-Authors: Pierre Hakizimana, William E. Brownell, Stefan Jacob, Anders FridbergerAbstract:Hearing relies on mechanical stimulation of stereocilia bundles on the sensory cells of the inner ear. When sound hits the ear, each Stereocilium pivots about a neck-like taper near their base. More than three decades of research have established that sideways deflection of stereocilia is essential for converting mechanical stimuli into electrical signals. Here we show that mammalian outer hair cell stereocilia not only move sideways but also change length during sound stimulation. Currents that enter stereocilia through mechanically sensitive ion channels control the magnitude of both length changes and bundle deflections in a reciprocal manner: the smaller the length change, the larger is the bundle deflection. Thus, the transduction current is important for maintaining the resting mechanical properties of stereocilia. Hair cell stimulation is most effective when bundles are in a state that ensures minimal length change.
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Sound‐Evoked Length Changes of the Outer Hair Cell Stereocilia Bundle are Modulated by Endocochlear Currents
2011Co-Authors: Pierre Hakizimana, William E. Brownell, Stefan Jacob, Anders FridbergerAbstract:The apical surface of vertebrate inner ear sensory cells is characterized by a bundle of giant microvilli commonly known as stereocilia. Stereocilia bend about a neck‐like thinning near their base and more than three decades of research has established that the direction and magnitude of sideways bundle deflection is the basis of the mechanoelectrical signalling that initiates sound perception. Aside from its ability to bend at the neck, the Stereocilium is usually considered as a stiff inelastic rod. Here we show that the length of OHC stereocilia changes during sound transduction, demonstrating their axial compliance, and that the magnitude of the length change is modulated by currents that mimic in vivo endocochlear currents. A reciprocal relation between length change and bundle deflection is evident: the smaller the length changes, the larger the bundle deflection.
Junha Song - One of the best experts on this subject based on the ideXlab platform.
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A cryo-tomography-based volumetric model of the actin core of mouse vestibular hair cell stereocilia lacking plastin 1.
Journal of structural biology, 2020Co-Authors: Junha Song, Roma Patterson, Jocelyn F. Krey, Samantha Hao, Linshanshan Wang, Salim Sazzed, Julio A. Kovacs, Zoltan Metlagel, Willy WriggersAbstract:Abstract Electron cryo-tomography allows for high-resolution imaging of stereocilia in their native state. Because their actin filaments have a higher degree of order, we imaged stereocilia from mice lacking the actin crosslinker plastin 1 (PLS1). We found that while stereocilia actin filaments run 13 nm apart in parallel for long distances, there were gaps of significant size that were stochastically distributed throughout the actin core. Actin crosslinkers were distributed through the Stereocilium, but did not occupy all possible binding sites. At stereocilia tips, protein density extended beyond actin filaments, especially on the side of the tip where a tip link is expected to anchor. Along the shaft, repeating density was observed that corresponds to actin-to-membrane connectors. In the taper region, most actin filaments terminated near the plasma membrane. The remaining filaments twisted together to make a tighter bundle than was present in the shaft region; the spacing between them decreased from 13 nm to 9 nm, and the apparent filament diameter decreased from 6.4 to 4.8 nm. Our models illustrate detailed features of distinct structural domains that are present within the Stereocilium.
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A cryo-tomography-based volumetric model of the actin core of mouse vestibular hair cell stereocilia lacking plastin 1
2019Co-Authors: Junha Song, Roma Patterson, Jocelyn F. Krey, Samantha Hao, Linshanshan Wang, Salim Sazzed, Julio A. Kovacs, Willy WriggersAbstract:Electron cryo-tomography allows for high-resolution imaging of stereocilia in their native state. Because their actin filaments have a higher degree of order, we imaged stereocilia from mice lacking the actin crosslinker plastin 1 (PLS1). We found that while stereocilia actin filaments run in parallel for long distances, 13 nm apart, there were gaps of significant size that were stochastically distributed throughout the actin core. Actin crosslinkers were distributed through the Stereocilium, but did not occupy all possible binding sites. At stereocilia tips, protein density extended beyond actin filaments, especially on the side of the tip where a tip link should anchor. Along the shaft, repeating density was observed that corresponds to actin-to-membrane connectors. In the taper region, most actin filaments terminated near the plasma membrane. The remaining filaments twisted together to make a tighter bundle than was present in the shaft region; the spacing between them decreased from 13 nm to 9 nm. Our models illustrate detailed features of distinct structural domains that are present within the Stereocilium.
