The Role of the Lysosomal Cl<sup>−</sup>/H<sup>+</sup> Antiporter ClC-7 in Osteopetrosis and Neurodegeneration
CLC proteins comprise Cl<sup>−</sup> channels and anion/H<sup>+</sup> antiporters involved in several fundamental physiological processes. ClC-7 is a lysosomal Cl<sup>−</sup>/H<sup>+</sup> antiporter that together with its beta subunit Ostm1 has a crit...
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| Format: | Article |
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MDPI AG
2022-01-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/3/366 |
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| author | Giovanni Zifarelli |
| author_facet | Giovanni Zifarelli |
| author_sort | Giovanni Zifarelli |
| collection | DOAJ |
| description | CLC proteins comprise Cl<sup>−</sup> channels and anion/H<sup>+</sup> antiporters involved in several fundamental physiological processes. ClC-7 is a lysosomal Cl<sup>−</sup>/H<sup>+</sup> antiporter that together with its beta subunit Ostm1 has a critical role in the ionic homeostasis of lysosomes and of the osteoclasts’ resorption lacuna, although the specific underlying mechanism has so far remained elusive. Mutations in ClC-7 cause osteopetrosis, but also a form of lysosomal storage disease and neurodegeneration. Interestingly, both loss-of- and gain-of-function mutations of ClC-7 can be pathogenic, but the mechanistic implications of this finding are still unclear. This review will focus on the recent advances in our understanding of the biophysical properties of ClC-7 and of its role in human diseases with a focus on osteopetrosis and neurodegeneration. |
| first_indexed | 2024-03-10T00:04:36Z |
| format | Article |
| id | doaj.art-b2d3c6eaa5074516a368f8703a06517c |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T00:04:36Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-b2d3c6eaa5074516a368f8703a06517c2023-11-23T16:10:39ZengMDPI AGCells2073-44092022-01-0111336610.3390/cells11030366The Role of the Lysosomal Cl<sup>−</sup>/H<sup>+</sup> Antiporter ClC-7 in Osteopetrosis and NeurodegenerationGiovanni Zifarelli0Institute of Biophysics—CNR, 16149 Genova, ItalyCLC proteins comprise Cl<sup>−</sup> channels and anion/H<sup>+</sup> antiporters involved in several fundamental physiological processes. ClC-7 is a lysosomal Cl<sup>−</sup>/H<sup>+</sup> antiporter that together with its beta subunit Ostm1 has a critical role in the ionic homeostasis of lysosomes and of the osteoclasts’ resorption lacuna, although the specific underlying mechanism has so far remained elusive. Mutations in ClC-7 cause osteopetrosis, but also a form of lysosomal storage disease and neurodegeneration. Interestingly, both loss-of- and gain-of-function mutations of ClC-7 can be pathogenic, but the mechanistic implications of this finding are still unclear. This review will focus on the recent advances in our understanding of the biophysical properties of ClC-7 and of its role in human diseases with a focus on osteopetrosis and neurodegeneration.https://www.mdpi.com/2073-4409/11/3/366chloride transportproton transportorganellar transporterlysosomal storage diseaseosteopetrosisbone |
| spellingShingle | Giovanni Zifarelli The Role of the Lysosomal Cl<sup>−</sup>/H<sup>+</sup> Antiporter ClC-7 in Osteopetrosis and Neurodegeneration Cells chloride transport proton transport organellar transporter lysosomal storage disease osteopetrosis bone |
| title | The Role of the Lysosomal Cl<sup>−</sup>/H<sup>+</sup> Antiporter ClC-7 in Osteopetrosis and Neurodegeneration |
| title_full | The Role of the Lysosomal Cl<sup>−</sup>/H<sup>+</sup> Antiporter ClC-7 in Osteopetrosis and Neurodegeneration |
| title_fullStr | The Role of the Lysosomal Cl<sup>−</sup>/H<sup>+</sup> Antiporter ClC-7 in Osteopetrosis and Neurodegeneration |
| title_full_unstemmed | The Role of the Lysosomal Cl<sup>−</sup>/H<sup>+</sup> Antiporter ClC-7 in Osteopetrosis and Neurodegeneration |
| title_short | The Role of the Lysosomal Cl<sup>−</sup>/H<sup>+</sup> Antiporter ClC-7 in Osteopetrosis and Neurodegeneration |
| title_sort | role of the lysosomal cl sup sup h sup sup antiporter clc 7 in osteopetrosis and neurodegeneration |
| topic | chloride transport proton transport organellar transporter lysosomal storage disease osteopetrosis bone |
| url | https://www.mdpi.com/2073-4409/11/3/366 |
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