The Role of the Lysosomal Cl−/H+ Antiporter ClC-7 in Osteopetrosis and Neurodegeneration

Cells

Giovanni Zifarelli¹ 

[1] Institute of Biophysics—CNR, 16149 Genova, Italy;

关键词: chloride transport;    proton transport;    organellar transporter;    lysosomal storage disease;    osteopetrosis;    bone;   

DOI  :  10.3390/cells11030366

来源: DOAJ

【 摘 要 】

CLC proteins comprise Cl⁻ channels and anion/H⁺ antiporters involved in several fundamental physiological processes. ClC-7 is a lysosomal Cl⁻/H⁺ 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.

【 授权许可】

Unknown