guest ::
| Home > Publications database > Metabolic energy sensing by mammalian CLC anion/proton exchangers |
| Home > Publications database > Metabolic energy sensing by mammalian CLC anion/proton exchangers |
| Journal Article | FZJ-2020-01948 |
; ; ; ;
2020
Wiley
Hoboken, NJ [u.a.]
This record in other databases: 
Please use a persistent id in citations: http://hdl.handle.net/2128/25110 doi:10.15252/embr.201947872
Abstract: CLC anion/proton exchangers control the pH and [Cl−] of the endolysosomal system that is essential for cellular nutrient uptake. Here, we use heterologous expression and whole‐cell electrophysiology to investigate the regulation of the CLC isoforms ClC‐3, ClC‐4, and ClC‐5 by the adenylic system components ATP , ADP , and AMP . Our results show that cytosolic ATP and ADP but not AMP and Mg2+‐free ADP enhance CLC ion transport. Biophysical analysis reveals that adenine nucleotides alter the ratio between CLC ion transport and CLC gating charge and shift the CLC voltage‐dependent activation. The latter effect is suppressed by blocking the intracellular entrance of the proton transport pathway. We suggest, therefore, that adenine nucleotides regulate the internal proton delivery into the CLC transporter machinery and alter the probability of CLC transporters to undergo silent non‐transporting cycles. Our findings suggest that the CBS domains in mammalian CLC transporters serve as energy sensors that regulate vesicular Cl−/H+ exchange by detecting changes in the cytosolic ATP /ADP /AMP equilibrium. Such sensing mechanism links the endolysosomal activity to the cellular metabolic state.
; 
; 
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection
|
The record appears in these collections: |
PDF
PDF (PDFA)