Development of the hair bundle and mechanotransduction

Nayak, Gowri; Ratnayaka, Helen Sum Kay; Goodyear, Richard J.; Richardson, Guy P.

doi:10.1387/ijdb.072392gn

Cited by 86 publications

(87 citation statements)

References 126 publications

(153 reference statements)

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“…The stereocilia muster into their oriented, serried ranks through a complex web of intra-and intercellular commands (17,18). Thus, it's no surprise that the proteins making up the MT complex will include essential elements in addition to those that form the channel pore.…”

Section: The Stereociliary Bundle Defines the Adequate Stimulusmentioning

confidence: 99%

How many proteins does it take to gate hair cell mechanotransduction?

Fuchs

2015

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

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Components of the Mechanotransducer ComplexMechanosensory hair cells of the inner ear transduce sound or head motion into electrical signals through the gating of mechanically coupled ion channels. Although many cell types can respond to mechanical force (1), the disposition of mechanotransduction (MT) channels to the very tips of stereocilia (2, 3) confers onto hair cells of the inner ear their specialized sensitivity (4, 5). Differential deflection of the stereociliary tips is transmitted to the MT channels via extracellular "tiplinks" that extend between taller and shorter stereocilia (6-8). The tip-links are composed of cadherin 23 and protocadherin 15 (5), the latter of which forms the lower end coupled to the MT gating complex. Positional cloning of a human deafness locus identified transmembrane channel-like protein isoforms (TMC)1 and TMC2 as potential components of the MT complex (9). TMC1 and TMC2 interact with protocadherin 15 (10) and have been nominated as subunits of the channel itself (11), perhaps combining differentially to generate the tonotopic variation in unitary conductance (larger in higher frequency hair cells) (12). The challenge for the field is to establish molecular mechanisms in a cellular organelle (the hair bundle) that couples extracellular force to channel gating through a still incompletely defined complement of interacting proteins. The problem is compounded by the fact that the MT channel and its binding partners must be transported and assembled at the stereociliary tips. In PNAS, Beurg et al. (13) shine a revealing light onto these complexities. The authors show that LHFPL5 (lipoma HMGIC fusion partnerlike 5, also known as tetraspan membrane protein of hair cell stereocilia, or TMHS) is required for normal MT current, apparently by regulating the participation of TMC1 (but not TMC2). These results in themselves help to keep the story of haircell MT moving forward. However, the authors' description of "reverse-polarity" MT currents puts an intriguing twist into the plot. Reverse-Polarity MechanotransductionThe cornerstone of hair-cell MT is its directional specificity. Deflection toward the taller stereocilia causes MT channel opening, cationic influx, and hair-cell depolarization; the opposite motion causes channel closure (4). Incredibly, hair cells of homozygous LHFPL5 null (LHFPL5 −/− ) mice generate Beurg et al. propose that LHFPL5 is required for correct positioning of TMC1 in the MT complex, and in particular for the tonotopic gradient in unitary conductance of the MT channel.reverse-polarity MT currents that can be even larger than those for the normal polarity motion. Reverse-polarity currents also have been reported for TMC1/TMC2 double mutants (14) and other MT-disrupted hair cells (15), keeping open the nomination process for MT channel proteins. Knockout of LHFPL5 produced smaller single MT channel currents and flattened the tonotopic gradient in unitary conductance (for normal polarity motion, reverse-polarity currents appear similar in low-and high-frequency ha...

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Section: The Stereociliary Bundle Defines the Adequate Stimulusmentioning

confidence: 99%

How many proteins does it take to gate hair cell mechanotransduction?

Fuchs

2015

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

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“…Finally, the stereocilia grow both in length and in width and reach their mature size. In rodent mature cochlear hair cells, the ankle links and the kinociliary links disappear with the regression of the kinocilium (Frolenkov et al, 2004;Goodyear et al, 2005;Nayak et al, 2007).…”

Section: Hair Bundle Cohesionmentioning

confidence: 99%

Usher Syndrome: Genes, Proteins, Models, Molecular Mechanisms, and Therapies

Yang¹

2012

Hearing Loss

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“…However, it appears that in the ear Atoh1 is unique in that it is both necessary and sufficient to generate hair cells (Raphael, 2007;this volume). How exactly the early expressed transcription factors tie into the specific hair cell and supporting cell histogenesis is currently unclear and an exhaustive overview of the current state of knowledge is provided in this volume (Kelley, 2007;Richardson, 2007).…”

Section: Cell Cycle Cell Determination and Differentiationmentioning

confidence: 99%

The molecular biology of ear development - "Twenty years are nothing"

Giráldez

Fritzsch²

2007

Int. J. Dev. Biol.

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Views of classical biological problems changed dramatically with the rise of molecular biology as a common framework. It was indeed the new language of life sciences. Molecular biology increasingly moved us towards a unified view of developmental genetics as ideas and techniques were imported to vertebrates from other biological systems where genetics was in a more advanced state. The ultimate advance has been the ability to actually perform genetic manipulations in vertebrate organisms that were almost unthinkable before. During the last two decades these technical advances entered into and affected the research on ear development. These events are still very recent and have been with us for no longer than two decades, which is the reason for the title of this article. This new scenario forms the basis of the current and productive work of many laboratories, and this is what this Special Issue of The International Journal of Developmental Biology wants to show, presenting a snapshot of insights at the beginning of the 21st Century. In this article, we give an overview of the topics that are addressed in this Ear Development Special Issue, and also we take the opportunity to informally dig into the genealogy of some of those topics, trying to link the current work with some classical work of the past. KEY WORDS: cell fate, patterning, hair cell, otic neuron, morphogenesis, evolution, regenerationEach time is characterised by the field of possibility that defines not only the standing theories or beliefs, but also the nature of the objects which are accessible to analysis, the means to look at them and the way to observe and to talk about them. (Jacob, 1976) There has been a sustained interest in ear developmental biology all throughout the 20 th century. As with many other fields in biology and neurosciences, this interest is in part rooted in curiosity and in part is driven by the intent to understand and cure diseases. There is an immense catalogue of histological observations and clever experimental manipulations of the embryonic ear that have contributed to an increase in our knowledge of the development of the ear and that was able to paint a picture of ear development by the end of the eighties (see Rubel, 1978; and the report of the Holte Symposium (Cremers et al., 1987). The view at the end of the eighties, however detailed, remained descriptive and phenomenological: the gap between cells, genes and proteins was Int. J. Dev. Biol. 51: 429-438 (2007) still too large and many processes were unknown leaving "the widest gap to be filled… to understanding how cells with identical genomes may become differentiated" (Jacob, 1947). Thirty years elapsed from the publishing of the double helix in 1953 to the polymerase chain reaction (Saiki et al., 1985) and during this period of time the whole of biology was changed and set a new paradigm. Views of classical biological problems, changed dramatically with the rise of molecular biology as a common framework. It was indeed the new language of life scien...

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Development of the hair bundle and mechanotransduction

Cited by 86 publications

References 126 publications

How many proteins does it take to gate hair cell mechanotransduction?

How many proteins does it take to gate hair cell mechanotransduction?

Usher Syndrome: Genes, Proteins, Models, Molecular Mechanisms, and Therapies

The molecular biology of ear development - "Twenty years are nothing"

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