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Ca²⁺ entry through mechanotransduction channels localizes BAIAP2L2 to stereocilia tips.

ABSTRACT: Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 2 (BAIAP2L2), a membrane-binding protein required for the maintenance of mechanotransduction in hair cells, is selectively retained at the tips of transducing stereocilia. BAIAP2L2 trafficked to stereocilia tips in the absence of EPS8, but EPS8 increased the efficiency of localization. A tripartite complex of BAIAP2L2, EPS8, and MYO15A formed efficiently in vitro, and these three proteins robustly targeted to filopodia tips when coexpressed in cultured cells. Mice lacking functional transduction channels no longer concentrated BAIAP2L2 at row 2 stereocilia tips, a result that was phenocopied by blocking channels with tubocurarine in cochlear explants. Transduction channels permit Ca²⁺ entry into stereocilia, and we found that membrane localization of BAIAP2L2 was enhanced in the presence of Ca²⁺. Finally, reduction of intracellular Ca²⁺ in hair cells using BAPTA-AM led to a loss of BAIAP2L2 at stereocilia tips. Taken together, our results show that a MYO15A-EPS8 complex transports BAIAP2L2 to stereocilia tips, and Ca²⁺ entry through open channels at row 2 tips retains BAIAP2L2 there.

SUBMITTER: Halford J

PROVIDER: S-EPMC9250357 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Human periodontal ligament (hPDL) fibroblasts are thought to receive mechanical stress (MS) produced by orthodontic tooth movement, thereby regulating alveolar bone remodeling. However, the role of intracellular calcium ([Ca2+]i)-based mechanotransduction is not fully understood. We explored the MS-induced [Ca2+]i responses both in isolated hPDL fibroblasts and in intact hPDL tissue and investigated its possible role in alveolar bone remodeling. hPDL fibroblasts were obtained from healthy donors' premolars that had been extracted for orthodontic reasons. The oscillatory [Ca2+]i activity induced by static compressive force was measured by a live-cell Ca2+ imaging system and evaluated by several feature extraction method. The spatial pattern of cell-cell communication was investigated by Moran's I, an index of spatial autocorrelation and the gap junction (GJ) inhibitor. The Ca2+-transporting ionophore A23187 was used to further investigate the role of [Ca2+]i up-regulation in hPDL cell behavior. hPDL fibroblasts displayed autonomous [Ca2+]i responses. Compressive MS activated this autonomous responsive behavior with an increased percentage of responsive cells both in vitro and ex vivo. The integration, variance, maximum amplitude, waveform length, and index J in the [Ca2+]i responses were also significantly increased, whereas the mean power frequency was attenuated in response to MS. The increased Moran's I after MS indicated that MS might affect the pattern of cell-cell communication via GJs. Similar to the findings of MS-mediated regulation, the A23187-mediated [Ca2+]i uptake resulted in the up-regulation of receptor activator of NF-κB ligand (Rankl) and Sost along with increased sclerostin immunoreactivity, suggesting that [Ca2+]i signaling networks may be involved in bone remodeling. In addition, A23187-treated hPDL fibroblasts also showed the suppression of osteogenic differentiation and mineralization. Our findings suggest that augmented MS-mediated [Ca2+]i oscillations in hPDL fibroblasts enhance the production and release of bone regulatory signals via Rankl/Osteoprotegerin and the canonical Wnt/β-catenin pathway as an early process in tooth movement-initiated alveolar bone remodeling.-Ei Hsu Hlaing, E., Ishihara, Y., Wang, Z., Odagaki, N., Kamioka, H. Role of intracellular Ca2+-based mechanotransduction of human periodontal ligament fibroblasts.

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Ca²⁺ entry through mechanotransduction channels localizes BAIAP2L2 to stereocilia tips.

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Dataset Information

Ca2+ entry through mechanotransduction channels localizes BAIAP2L2 to stereocilia tips.

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OmicsDI is part of the ELIXIR infrastructure

Tweets

Ca²⁺ entry through mechanotransduction channels localizes BAIAP2L2 to stereocilia tips.