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Controllable Ion Channel Expression through Inducible Transient Transfection
Published on: February 17, 2017
Extracellular pH dynamically controls cell surface delivery of functional TRPV5 channels
Tim T Lambers1, Elena Oancea, Theun de Groot
1Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands.
Molecular and Cellular Biology
|December 21, 2006
Summary
Extracellular pH regulates calcium channel TRPV5 cell surface expression. Vesicles containing TRPV5 channels transiently interact with the cell membrane, controlling calcium transport.
Area of Science:
- Cell Biology
- Physiology
- Biophysics
Background:
- Extracellular pH influences ion transport and ion channel activity.
- The Ca(2+)-selective transient receptor potential vanilloid 5 (TRPV5) channel is crucial for calcium homeostasis.
- TRPV5 functions as the apical gate for calcium entry in transporting cells.
Purpose of the Study:
- To investigate the mechanism by which extracellular pH affects TRPV5 cell surface expression.
- To elucidate the role of vesicular trafficking in TRPV5 regulation.
- To understand the dynamic interaction of TRPV5 with the plasma membrane in response to pH changes.
Main Methods:
- Total internal reflection fluorescence microscopy (TIR-FM)
- Cell surface protein labeling
- Electrophysiology
- (45)Ca(2+) uptake assays
- Functional channel recovery after chemobleaching
Main Results:
- Extracellular alkalinization rapidly recruits TRPV5-containing vesicles to the cell surface.
- These vesicles contain functional TRPV5 channels, leading to increased TRPV5 activity.
- Extracellular acidification causes vesicle retrieval, decreasing TRPV5 activity.
- TRPV5 channels access the extracellular space through transient vesicular "kiss and linger" events.
Conclusions:
- Extracellular pH dynamically regulates TRPV5 cell surface expression and activity via vesicular trafficking.
- TRPV5 channels utilize a "kiss and linger" mechanism for transient plasma membrane interactions.
- This vesicular mechanism enables rapid cellular responses of constitutive active TRP channels to physiological stimuli like pH changes.
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