Radixin modulates the function of outer hair cell stereocilia

Prasad, Sonal; Vona, Barbara; Diñeiro, Marta; Costales, María; González-Aguado, Rocío; Fontalba, Ana; Diego-Pérez, Clara; Subaşıoğlu, Aslı; Bademci, Güney; Tekin, Mustafa; Cabanillas, Rubén; Cadiñanos, Juan; Fridberger, Anders

doi:10.1038/s42003-020-01506-y

Cited by 6 publications

(6 citation statements)

References 41 publications

(59 reference statements)

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“…Stereocilia are rich in cross-linked actin filaments, which provide the scaffold for the hair-like morphology of stereocilia. Rdx is highly enriched in stereocilia of inner and outer hair cells (Figure 1C) and critically supports the transduction function of stereocilia (Kitajiri et al, 2004;Pataky et al, 2004;Prasad et al, 2020). Specifically, Rdx (in its active conformation) links up transmembrane proteins (e.g.…”

Section: Introductionsupporting

confidence: 57%

“…Autosomal recessive deafness is linked to homozygous mutations in the human rdx gene ( Khan et al, 2007 ; Shearer et al, 2009 ; Bai et al, 2019 ; Prasad et al, 2020 ) affecting different domains of the protein ( Figure 1A ). In line with this, homozygous (−/−) rdx knockout mice suffer from a developmental degeneration of cochlear hair cell stereocilia that leads to hearing loss ( Kitajiri et al, 2004 ).…”

Section: Resultsmentioning

confidence: 99%

“…We therefore conclude that 50% rdx gene dosage and protein expression levels are in general sufficient for cochlea development and stimuli transduction. On the other hand, a recent study reported an impairment of outer hair cell stereocilia function in guinea pigs, following chemical inhibition of Rdx ( Prasad et al, 2020 ). In this study, the authors specifically disrupted radixin’s ability to link F-actin with the plasma membrane, leading to decreased sound-evoked electrical potentials.…”

Section: Discussionmentioning

confidence: 99%

“…The ERM-family and actin-binding protein radixin are candidate molecular regulators of proper hearing. Mutations in the rdx gene encoding radixin (Rdx) ( Figure 1A ) cause non-syndromic hearing loss (DFNB24; OMIM # 611022 ) in human patients ( Khan et al, 2007 ; Shearer et al, 2009 ; Bai et al, 2019 ; Prasad et al, 2020 ). Moreover, the homozygous loss of rdx causes deafness in mice as result of stereocilia hair bundle degeneration ( Kitajiri et al, 2004 ).…”

Section: Introductionmentioning

confidence: 99%

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Monoallelic loss of the F-actin-binding protein radixin facilitates startle reactivity and pre-pulse inhibition in mice

Hausrat

Vogl

Neef

et al. 2022

Front. Cell Dev. Biol.

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Hearing impairment is one of the most common disorders with a global burden and increasing prevalence in an ever-aging population. Previous research has largely focused on peripheral sensory perception, while the brain circuits of auditory processing and integration remain poorly understood. Mutations in the rdx gene, encoding the F-actin binding protein radixin (Rdx), can induce hearing loss in human patients and homozygous depletion of Rdx causes deafness in mice. However, the precise physiological function of Rdx in hearing and auditory information processing is still ill-defined. Here, we investigated consequences of rdx monoallelic loss in the mouse. Unlike the homozygous (−/−) rdx knockout, which is characterized by the degeneration of actin-based stereocilia and subsequent hearing loss, our analysis of heterozygous (+/−) mutants has revealed a different phenotype. Specifically, monoallelic loss of rdx potentiated the startle reflex in response to acoustic stimulation of increasing intensities, suggesting a gain of function relative to wildtype littermates. The monoallelic loss of the rdx gene also facilitated pre-pulse inhibition of the acoustic startle reflex induced by weak auditory pre-pulse stimuli, indicating a modification to the circuit underlying sensorimotor gating of auditory input. However, the auditory brainstem response (ABR)-based hearing thresholds revealed a mild impairment in peripheral sound perception in rdx (+/-) mice, suggesting minor aberration of stereocilia structural integrity. Taken together, our data suggest a critical role of Rdx in the top-down processing and/or integration of auditory signals, and therefore a novel perspective to uncover further Rdx-mediated mechanisms in central auditory information processing.

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Section: Introductionsupporting

confidence: 57%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Monoallelic loss of the F-actin-binding protein radixin facilitates startle reactivity and pre-pulse inhibition in mice

Hausrat

Vogl

Neef

et al. 2022

Front. Cell Dev. Biol.

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“…Ezrin may support the initial formation of the stereocilia, but its expression is not maintained in adulthood (Kitajiri et al, 2004). Another ERM protein, radixin (RDX), is localized around the base of hair cell stereocilia and blocking RDX function results in increased deflection but reduced sensitivity in response to sound (Pataky et al, 2004; Prasad et al, 2020).…”

Section: Microvillar Actin Cytoskeletonmentioning

confidence: 99%

The morphological and functional diversity of apical microvilli

et al. 2022

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Sensory neurons use specialized apical processes to perceive external stimuli and monitor internal body conditions. The apical apparatus can include cilia, microvilli, or both, and is adapted for the functions of the particular cell type. Photoreceptors detect light through a large, modified cilium (outer segment), that is supported by a surrounding ring of microvilli-like calyceal processes (CPs). Although first reported 150 years ago, CPs remain poorly understood. As a basis for future study, we therefore conducted a review of existing literature about sensory cell microvilli, which can act either as the primary sensory detector or as support for a cilia-based detector. While all microvilli are finger-like cellular protrusions with an actin core, the processes vary across cell types in size, number, arrangement, dynamics, and function. We summarize the current state of knowledge about CPs and the characteristics of the microvilli found on inner ear hair cells (stereocilia) and cerebral spinal fluid-contacting neurons, with comparisons to the brush border of the intestinal and renal epithelia. The structure, stability, and dynamics of the actin core are regulated by a complement of actin-binding proteins, which includes both common components and unique features when compared across cell types. Further, microvilli are often supported by lateral links, a glycocalyx, and a defined extracellular matrix, each adapted to the function and environment of the cell. Our comparison of microvillar features will inform further research into how CPs support photoreceptor function, and also provide a general basis for investigations into the structure and functions of apical microvilli found on sensory neurons.

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Liquid Metal‐Based High‐Density Interconnect Technology for Stretchable Printed Circuits

Wang,

Prasad,

Hellman

et al. 2023

Adv Funct Materials

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High‐density interconnect (HDI) technology for liquid metal (LM)‐based stretchable printed circuit boards is crucial for expanding their applicability. HDI technology provides high‐resolution multilayer circuits with a high density of components, as required for next generation of neuroprobes and ultrasonic and sensor arrays. This study presents a HDI technique utilizing laser engraved micro grooves in silicone with a protective lift‐off mask of polyvinyl alcohol (PVA) and subsequent microscale LM particle spray deposition. This approach achieves high‐resolution LM patterns and enables multilayer connectivity and high‐density integration of components simultaneously, that is, realizing HDI technology. It is demonstrated using a stretchable 0201 LED display with a density of six leads per mm2 and a cochlear implant (CI) electrode array. The demonstrated manufacturing of the CI has the potential to enable fully automated printed circuit board manufacturing of such implants with increased precision and throughput. Implants in guinea pigs show that the CI is capable of activating the auditory neuron with electrical auditory brainstem response (eABR) and electrical compound action potential (eCAP) of high quality. Moreover, the U‐shaped cross section of the LM interconnects provides a higher mechanical shock resistance of the circuit than that of normal rectangular cross sections.

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Radixin modulates the function of outer hair cell stereocilia

Cited by 6 publications

References 41 publications

Monoallelic loss of the F-actin-binding protein radixin facilitates startle reactivity and pre-pulse inhibition in mice

Monoallelic loss of the F-actin-binding protein radixin facilitates startle reactivity and pre-pulse inhibition in mice

The morphological and functional diversity of apical microvilli

Liquid Metal‐Based High‐Density Interconnect Technology for Stretchable Printed Circuits

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