The actin cytoskeleton in hair bundle development and hearing loss

Park, James; Bird, Jonathan E.

doi:10.1016/j.heares.2023.108817

Cited by 11 publications

(6 citation statements)

References 212 publications

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“…Whereas the physiological roles of canonical apical specializations such as the brush border and hair bundle are well established (solute uptake and mechanosensation, respectively) [63, 64], how the apical tuft supports the functions of the tuft cell remains unclear. We reasoned that by developing insight on the architecture of the tuft and its underlying cytoskeleton, we could begin to hypothesize how this structure might be leveraged in vivo to promote tuft cell function and intestinal homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Intestinal tuft cells assemble a cytoskeletal superstructure composed of co-aligned actin bundles and microtubules

Silverman,

Krystofiak,

Caplan

et al. 2024

Preprint

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All tissues consist of a distinct set of cell types, which collectively support organ function and homeostasis. Tuft cells are a rare epithelial cell type found in diverse epithelia, where they play important roles in sensing antigens and stimulating downstream immune responses. Exhibiting a unique polarized morphology, tuft cells are defined by an array of giant actin filament bundles that support ~2 microns of apical membrane protrusion and extend over 7 microns towards the perinuclear region. Despite their established roles in maintaining intestinal epithelial homeostasis, tuft cells remain understudied due to their rarity. Details regarding the ultrastructural organization of the tuft cell cytoskeleton, the molecular components involved in building the array of giant actin bundles, and how these cytoskeletal structures support tuft cell biology remain unclear. To begin to answer these questions, we used advanced light and electron microscopy to perform quantitative morphometry of the small intestinal tuft cell cytoskeleton. We found that tuft cell core bundles consist of actin filaments that are crosslinked in a parallel barbed-end out configuration. These polarized structures are also supported by a unique group of tuft cell enriched actin-binding proteins that are differentially localized along the giant core bundles. Furthermore, we found that tuft cell actin bundles are co-aligned with a highly ordered network of microtubules. Tuft cells assemble a cytoskeletal superstructure that is well positioned to serve as a track for subcellular transport along the apical-basolateral axis and in turn, support the dynamic sensing functions that are critical for intestinal epithelial homeostasis.

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Section: Discussionmentioning

confidence: 99%

Intestinal tuft cells assemble a cytoskeletal superstructure composed of co-aligned actin bundles and microtubules

Silverman,

Krystofiak,

Caplan

et al. 2024

Preprint

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“…A number of highly specialized proteins are responsible for stereocilia assembly and function during acoustic stimulation and these also provide mechanical stiffening and anchorage to the cuticular plate. Tightly packed parallel arrangements of actin microfilaments provide mechanical support to the stereo-cilia ( Park and Bird 2023 ) however the upper region of the stereocilia is stabilized by interactions between the cytoplasmic tail of cadherin 23 and its actin anchoring protein harmonin forming large protein aggregates attached to the cytoskeleton providing mechanical support and control of the gating properties of the MET channels in the tip of the stereocilia ( Wu et al. 2012 ).…”

Section: Ks Facilitates Electrolocation An Ultrasensitive Sensory Mod...mentioning

confidence: 99%

Keratan sulfate, an electrosensory neurosentient bioresponsive cell instructive glycosaminoglycan

Melrose

2024

Glycobiology

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The roles of keratan sulfate (KS) as a proton detection glycosaminoglycan in neurosensory processes in the central and peripheral nervous systems is reviewed. The functional properties of the KS-proteoglycans aggrecan, phosphacan, podocalyxcin as components of perineuronal nets in neurosensory processes in neuronal plasticity, cognitive learning and memory are also discussed. KS-glycoconjugate neurosensory gels used in electrolocation in elasmobranch fish species and KS substituted mucin like conjugates in some tissue contexts in mammals need to be considered in sensory signalling. Parallels are drawn between KS’s roles in elasmobranch fish neurosensory processes and its roles in mammalian electro mechanical transduction of acoustic liquid displacement signals in the cochlea by the tectorial membrane and stereocilia of sensory inner and outer hair cells into neural signals for sound interpretation. The sophisticated structural and functional proteins which maintain the unique high precision physical properties of stereocilia in the detection, transmittance and interpretation of acoustic signals in the hearing process are important. The maintenance of the material properties of stereocilia are essential in sound transmission processes. Specific, emerging roles for low sulfation KS in sensory bioregulation are contrasted with the properties of high charge density KS isoforms. Some speculations are made on how the molecular and electrical properties of KS may be of potential application in futuristic nanoelectronic, memristor technology in advanced ultrafast computing devices with low energy requirements in nanomachines, nanobots or molecular switches which could be potentially useful in artificial synapse development. Application of KS in such innovative areas in bioregulation are eagerly awaited.

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“…The turnover of actin is seminal for the functional micro-anatomy of SC. In fact, the hair bundle in each HC is composed of roughly 100 SC with progressive length and width [79]. Despite being apparently simple, the architecture of HC SC is complex to maintain effective MET activity.…”

Section: The Role Of Autophagy In Maintaining the Structure Of Ohc Sc...mentioning

confidence: 99%

The Relevance of Autophagy within Inner Ear in Baseline Conditions and Tinnitus-Related Syndromes

Lazzeri,

Biagioni,

Ferrucci

et al. 2023

IJMS

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Tinnitus is the perception of noise in the absence of acoustic stimulation (phantom noise). In most patients suffering from chronic peripheral tinnitus, an alteration of outer hair cells (OHC) starting from the stereocilia (SC) occurs. This is common following ototoxic drugs, sound-induced ototoxicity, and acoustic degeneration. In all these conditions, altered coupling between the tectorial membrane (TM) and OHC SC is described. The present review analyzes the complex interactions involving OHC and TM. These need to be clarified to understand which mechanisms may underlie the onset of tinnitus and why the neuropathology of chronic degenerative tinnitus is similar, independent of early triggers. In fact, the fine neuropathology of tinnitus features altered mechanisms of mechanic-electrical transduction (MET) at the level of OHC SC. The appropriate coupling between OHC SC and TM strongly depends on autophagy. The involvement of autophagy may encompass degenerative and genetic tinnitus, as well as ototoxic drugs and acoustic trauma. Defective autophagy explains mitochondrial alterations and altered protein handling within OHC and TM. This is relevant for developing novel treatments that stimulate autophagy without carrying the burden of severe side effects. Specific phytochemicals, such as curcumin and berberin, acting as autophagy activators, may mitigate the neuropathology of tinnitus.

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The actin cytoskeleton in hair bundle development and hearing loss

Cited by 11 publications

References 212 publications

Intestinal tuft cells assemble a cytoskeletal superstructure composed of co-aligned actin bundles and microtubules

Intestinal tuft cells assemble a cytoskeletal superstructure composed of co-aligned actin bundles and microtubules

Keratan sulfate, an electrosensory neurosentient bioresponsive cell instructive glycosaminoglycan

The Relevance of Autophagy within Inner Ear in Baseline Conditions and Tinnitus-Related Syndromes

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