Ca<sup>2+</sup> entry through mechanotransduction channels localizes BAIAP2L2 to stereocilia tips

Halford, Julia; Bateschell, Michael; Barr-Gillespie, Peter G.

doi:10.1091/mbc.e21-10-0491

Cited by 8 publications

(10 citation statements)

References 50 publications

(151 reference statements)

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“…BAIAP2L2 (also known as pinkbar) localizes to the tips of short stereocilia in cochlear hair cells, and both conditional and full knockout mouse mutants show progressive stereocilia degeneration and hearing loss (Carlton et al, 2021; Yan et al, 2021). BAIAP2L2 is transported to the tips in a complex with EPS8 and MYO15A (long isoform) and appears after the stereocilia have already formed (Carlton et al, 2021; Halford et al, 2022). Subsequently, MET channel activity is required to maintain BAIAP2L2 at the tips, possibly through Ca 2+ influx and/or binding to the channel subunit CIB2 (Halford et al, 2022; Yan et al, 2021).…”

Section: Microvillar Actin Cytoskeletonmentioning

confidence: 99%

“…BAIAP2L2 is transported to the tips in a complex with EPS8 and MYO15A (long isoform) and appears after the stereocilia have already formed (Carlton et al, 2021;Halford et al, 2022). Subsequently, MET channel activity is required to maintain BAIAP2L2 at the tips, possibly through Ca 2+ influx and/or binding to the channel subunit CIB2 (Halford et al, 2022;Yan et al, 2021). Notably, BAIAP2L2 has a unique almost-flat membrane-binding surface, which may better suit it for the wide morphology of stereocilia.…”

Section: Actin-membrane Connectionsmentioning

confidence: 99%

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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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Section: Microvillar Actin Cytoskeletonmentioning

confidence: 99%

Section: Actin-membrane Connectionsmentioning

confidence: 99%

The morphological and functional diversity of apical microvilli

et al. 2022

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“…Several proteins concentrate at tips of row 2 stereocilia in developing hair bundles, including EPS8L2, ESPNL, BAIAP2L2, CAPZB, TWF2, DSTN and CFL1, and the locations of most of these are regulated by mechanotransduction 33–38 . We examined the location of two of these, EPS8L2 and CAPZB, in Ush1g bw hair cells.…”

Section: Resultsmentioning

confidence: 99%

Spontaneous allelic variant in deafness–blindness gene Ush1g resulting in an expanded phenotype

Vartanian

Krey

Chatterjee

et al. 2023

Genes Brain and Behavior

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Relationships between novel phenotypic behaviors and specific genetic alterations are often discovered using target‐specific, directed mutagenesis or phenotypic selection following chemical mutagenesis. An alternative approach is to exploit deficiencies in DNA repair pathways that maintain genetic integrity in response to spontaneously induced damage. Mice deficient in the DNA glycosylase NEIL1 show elevated spontaneous mutations, which arise from translesion DNA synthesis past oxidatively induced base damage. Several litters of Neil1 knockout mice included animals that were distinguished by their backwards‐walking behavior in open‐field environments, while maintaining frantic forward movements in their home cage environment. Other phenotypic manifestations included swim test failures, head tilting and circling. Mapping of the mutation that conferred these behaviors showed the introduction of a stop codon at amino acid 4 of the Ush1g gene. Ush1gbw/bw null mice displayed auditory and vestibular defects that are commonly seen with mutations affecting inner‐ear hair‐cell function, including a complete lack of auditory brainstem responses and vestibular‐evoked potentials. As in other Usher syndrome type I mutant mouse lines, hair cell phenotypes included disorganized and split hair bundles, as well as altered distribution of proteins for stereocilia that localize to the tips of row 1 or row 2. Disruption to the bundle and kinocilium displacement suggested that USH1G is essential for forming the hair cell's kinocilial links. Consistent with other Usher type 1 models, Ush1gbw/bw mice had no substantial retinal degeneration compared with Ush1gbw/+ controls. In contrast to previously described Ush1g alleles, this new allele provides the first knockout model for this gene.

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“…Several proteins concentrate at tips of row 2 stereocilia in developing hair bundles, including EPS8L2, ESPNL, BAIAP2L2, CAPZB, TWF2, DSTN, and CFL1, and the locations of most of these are regulated by mechanotransduction [30][31][32][33][34][35] . We examined the location of two of these, EPS8L2 and CAPZB, in Ush1g bw hair cells.…”

Section: Distribution Of Row-specific Proteins In Cochlear Hair Cellsmentioning

confidence: 99%

Spontaneous allelic variant inUsh1gresulting in an expanded phenotype

Vartanian

Krey

Chatterjee

et al. 2023

Preprint

Self Cite

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Strategies to reveal the discovery of the relationships between novel phenotypic behaviors and specific genetic alterations can be achieved via either target-specific, directed mutagenesis or phenotypic selection following random chemical mutagenesis. As an alternative approach, one can exploit deficiencies in DNA repair pathways that are responsible for the maintenance of genetic integrity in response to spontaneously-induced damage. In the genetic background of mice deficient in the DNA glycosylase NEIL1, elevated numbers of spontaneous mutations arise from translesion DNA synthesis past unrepaired, oxidatively-induced base damage. Several litters ofNeil1knockout mice included animals that were distinguished by their backwards-walking behavior in open-field environments, while maintaining frantic forward movements in their home cage environment. Other phenotypic manifestations included swim test failures, head tilting, and circling. Mapping of the mutation that conferred these behaviors revealed the introduction of a stop codon at amino acid 4 of theUsh1ggene; the allele wasUsh1gbw, reflecting the backwards-walking phenotype.Ush1gbw/bwnull mice displayed auditory and vestibular defects that are commonly seen with mutations affecting inner-ear hair-cell function, including a complete lack of auditory brainstem responses and vestibular-evoked potentials. As in other Usher syndrome type I mutant mouse lines, hair-cell phenotypes included disorganized and split hair bundles, as well as altered distribution of proteins for stereocilia that localize to the tips of row 1 or row 2. Disruption to the bundle and kinocilium displacement suggested that USH1G is essential for forming the hair cell’s kinocilial links. Due to the vestibular dysfunction, however, visual behavior as measured with optokinetic tracking could not be assessed inUsh1gbw/bwmice. Consistent with other Usher type 1 models, however,Ush1gbw/bwmice had no substantial retinal degeneration compared toUsh1gbw/+controls out to six months. In contrast to previously-describedUsh1galleles, this new allele provides the first knockout model for this gene.

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Ca²⁺ entry through mechanotransduction channels localizes BAIAP2L2 to stereocilia tips

Cited by 8 publications

References 50 publications

The morphological and functional diversity of apical microvilli

The morphological and functional diversity of apical microvilli

Spontaneous allelic variant in deafness–blindness gene Ush1g resulting in an expanded phenotype

Spontaneous allelic variant inUsh1gresulting in an expanded phenotype

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Ca2+ entry through mechanotransduction channels localizes BAIAP2L2 to stereocilia tips

Cited by 8 publications

References 50 publications

The morphological and functional diversity of apical microvilli

The morphological and functional diversity of apical microvilli

Spontaneous allelic variant in deafness–blindness gene Ush1g resulting in an expanded phenotype

Spontaneous allelic variant inUsh1gresulting in an expanded phenotype

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Ca²⁺ entry through mechanotransduction channels localizes BAIAP2L2 to stereocilia tips