Reference - Detail
| RRC ID | 80847 |
|---|---|
| Author | Zhang Q, Li Y, Jian Y, Li M, Wang X. |
| Title | Lysosomal chloride transporter CLH-6 protects lysosome membrane integrity via cathepsin activation. |
| Journal | J Cell Biol |
| Abstract |
Lysosomal integrity is vital for cell homeostasis, but the underlying mechanisms are poorly understood. Here, we identify CLH-6, the C. elegans ortholog of the lysosomal Cl-/H+ antiporter ClC-7, as an important factor for protecting lysosomal integrity. Loss of CLH-6 affects lysosomal degradation, causing cargo accumulation and membrane rupture. Reducing cargo delivery or increasing CPL-1/cathepsin L or CPR-2/cathepsin B expression suppresses these lysosomal defects. Inactivation of CPL-1 or CPR-2, like CLH-6 inactivation, affects cargo digestion and causes lysosomal membrane rupture. Thus, loss of CLH-6 impairs cargo degradation, leading to membrane damage of lysosomes. In clh-6(lf) mutants, lysosomes are acidified as in wild type but contain lower chloride levels, and cathepsin B and L activities are significantly reduced. Cl- binds to CPL-1 and CPR-2 in vitro, and Cl- supplementation increases lysosomal cathepsin B and L activities. Altogether, these findings suggest that CLH-6 maintains the luminal chloride levels required for cathepsin activity, thus facilitating substrate digestion to protect lysosomal membrane integrity. |
| Volume | 222(6) |
| Published | 2023-6-5 |
| DOI | 10.1083/jcb.202210063 |
| PII | 214033 |
| PMID | 37058288 |
| PMC | PMC10114921 |
| MeSH | Animals Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Cathepsin B* / metabolism Chloride Channels* / genetics Chloride Channels* / metabolism Chlorides / metabolism Intracellular Membranes / metabolism Lysosomes* / metabolism |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 50 |
| Altmetric score changes over past 6months | 0.2 |
| Resource | |
| C.elegans | tm617 tm6474 |