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DOI10.1073/pnas.2101378118
An otopetrin family proton channel promotes cellular acid efflux critical for biomineralization in a marine calcifier
Chang W.W.; Matt A.-S.; Schewe M.; Musinszki M.; Grüssel S.; Brandenburg J.; Garfield D.; Bleich M.; Baukrowitz T.; Hu M.Y.
发表日期2021
ISSN0027-8424
卷号118期号:30
英文摘要Otopetrins comprise a family of proton-selective channels that are critically important for the mineralization of otoliths and statoconia in vertebrates but whose underlying cellular mechanisms remain largely unknown. Here, we demonstrate that otopetrins are critically involved in the calcification process by providing an exit route for protons liberated by the formation of CaCO3. Using the sea urchin larva, we examined the otopetrin ortholog otop2l, which is exclusively expressed in the calcifying primary mesenchymal cells (PMCs) that generate the calcitic larval skeleton. otop2l expression is stimulated during skeletogenesis, and knockdown of otop2l impairs spicule formation. Intracellular pH measurements demonstrated Zn2+-sensitive H+ fluxes in PMCs that regulate intracellular pH in a Na+/HCO3−-independent manner, while Otop2l knockdown reduced membrane proton permeability. Furthermore, Otop2l displays unique features, including strong activation by high extracellular pH (>8.0) and check-valve–like outwardly rectifying H+ flux properties, making it into a cellular proton extrusion machine adapted to oceanic living conditions. Our results provide evidence that otopetrin family proton channels are a central component of the cellular pH regulatory machinery in biomineralizing cells. Their ubiquitous occurrence in calcifying systems across the animal kingdom suggest a conserved physiological function by mediating pH at the site of mineralization. This important role of otopetrin family proton channels has strong implications for our view on the cellular mechanisms of biomineralization and their response to changes in oceanic pH. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Calcification; Cell physiology; Intracellular pH; Ocean acidification; Sea urchin
语种英语
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/238459
作者单位Institute of Physiology, Christian-Albrechts-University of Kiel, Kiel, 24118, Germany; Integrative Research Institute for the Life Sciences, Humboldt-Universität zu Berlin, Berlin, 10117, Germany
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Chang W.W.,Matt A.-S.,Schewe M.,et al. An otopetrin family proton channel promotes cellular acid efflux critical for biomineralization in a marine calcifier[J],2021,118(30).
APA Chang W.W..,Matt A.-S..,Schewe M..,Musinszki M..,Grüssel S..,...&Hu M.Y..(2021).An otopetrin family proton channel promotes cellular acid efflux critical for biomineralization in a marine calcifier.Proceedings of the National Academy of Sciences of the United States of America,118(30).
MLA Chang W.W.,et al."An otopetrin family proton channel promotes cellular acid efflux critical for biomineralization in a marine calcifier".Proceedings of the National Academy of Sciences of the United States of America 118.30(2021).
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