This title appears in the Scientific Report :
2020
Please use the identifier:
http://dx.doi.org/10.15252/embr.201947872 in citations.
Please use the identifier: http://hdl.handle.net/2128/25110 in citations.
Metabolic energy sensing by mammalian CLC anion/proton exchangers
Metabolic energy sensing by mammalian CLC anion/proton exchangers
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 comp...
Saved in:
Personal Name(s): | Grieschat, Matthias |
---|---|
Guzman, Raul E / Langschwager, Katharina / Fahlke, Christoph / Alekov, Alexi K (Corresponding author) | |
Contributing Institute: |
Molekular- und Zellphysiologie; IBI-1 |
Published in: | EMBO reports, 21 (2020) 6, S. e47872 |
Imprint: |
Hoboken, NJ [u.a.]
Wiley
2020
|
DOI: |
10.15252/embr.201947872 |
PubMed ID: |
32390228 |
Document Type: |
Journal Article |
Research Program: |
Engineering Cell Function |
Link: |
OpenAccess OpenAccess |
Publikationsportal JuSER |
Please use the identifier: http://hdl.handle.net/2128/25110 in citations.
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. |