Cargando…

Ca(2+) entry through mechanotransduction channels localizes BAIAP2L2 to stereocilia tips

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Halford, Julia, Bateschell, Michael, Barr-Gillespie, Peter G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250357/
https://www.ncbi.nlm.nih.gov/pubmed/35044843
http://dx.doi.org/10.1091/mbc.E21-10-0491
_version_ 1784739796388675584
author Halford, Julia
Bateschell, Michael
Barr-Gillespie, Peter G.
author_facet Halford, Julia
Bateschell, Michael
Barr-Gillespie, Peter G.
author_sort Halford, Julia
collection PubMed
description 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 Ca(2+) entry into stereocilia, and we found that membrane localization of BAIAP2L2 was enhanced in the presence of Ca(2+). Finally, reduction of intracellular Ca(2+) 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 Ca(2+) entry through open channels at row 2 tips retains BAIAP2L2 there.
format Online
Article
Text
id pubmed-9250357
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher The American Society for Cell Biology
record_format MEDLINE/PubMed
spelling pubmed-92503572022-07-07 Ca(2+) entry through mechanotransduction channels localizes BAIAP2L2 to stereocilia tips Halford, Julia Bateschell, Michael Barr-Gillespie, Peter G. Mol Biol Cell Brief Reports 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 Ca(2+) entry into stereocilia, and we found that membrane localization of BAIAP2L2 was enhanced in the presence of Ca(2+). Finally, reduction of intracellular Ca(2+) 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 Ca(2+) entry through open channels at row 2 tips retains BAIAP2L2 there. The American Society for Cell Biology 2022-03-29 /pmc/articles/PMC9250357/ /pubmed/35044843 http://dx.doi.org/10.1091/mbc.E21-10-0491 Text en © 2022 Halford et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial-Share Alike 4.0 International Creative Commons License.
spellingShingle Brief Reports
Halford, Julia
Bateschell, Michael
Barr-Gillespie, Peter G.
Ca(2+) entry through mechanotransduction channels localizes BAIAP2L2 to stereocilia tips
title Ca(2+) entry through mechanotransduction channels localizes BAIAP2L2 to stereocilia tips
title_full Ca(2+) entry through mechanotransduction channels localizes BAIAP2L2 to stereocilia tips
title_fullStr Ca(2+) entry through mechanotransduction channels localizes BAIAP2L2 to stereocilia tips
title_full_unstemmed Ca(2+) entry through mechanotransduction channels localizes BAIAP2L2 to stereocilia tips
title_short Ca(2+) entry through mechanotransduction channels localizes BAIAP2L2 to stereocilia tips
title_sort ca(2+) entry through mechanotransduction channels localizes baiap2l2 to stereocilia tips
topic Brief Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250357/
https://www.ncbi.nlm.nih.gov/pubmed/35044843
http://dx.doi.org/10.1091/mbc.E21-10-0491
work_keys_str_mv AT halfordjulia ca2entrythroughmechanotransductionchannelslocalizesbaiap2l2tostereociliatips
AT bateschellmichael ca2entrythroughmechanotransductionchannelslocalizesbaiap2l2tostereociliatips
AT barrgillespiepeterg ca2entrythroughmechanotransductionchannelslocalizesbaiap2l2tostereociliatips