Extracellular Ph Dynamically Controls Cell Surface Delivery of Functional Trpv5 Channels.
From: Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands.
Molecular and cellular biology
- Publish Date: Feb 2007
- ISSN: 0270-7306
- Volume: 27
- Issue: 4
- Pages: 1486-94
- Medium: Print
- Language: English
- Citation (JAMA): Lambers Tim T, Oancea Elena, de Groot Theun, et al. Extracellular Ph Dynamically Controls Cell Surface Delivery of Functional Trpv5 Channels.. Mol. Cell. Biol. Feb 2007;27:1486-94
Abstract
Extracellular pH has long been known to affect the rate and magnitude of ion transport processes among others via regulation of ion channel activity. The Ca(2+)-selective transient receptor potential vanilloid 5 (TRPV5) channel constitutes the apical entry gate in Ca(2+)-transporting cells, contributing significantly to the overall Ca(2+) balance. Here, we demonstrate that extracellular pH determines the cell surface expression of TRPV5 via a unique mechanism. By a comprehensive approach using total internal reflection fluorescence microscopy, cell surface protein labeling, electrophysiology, (45)Ca(2+) uptake assays, and functional channel recovery after chemobleaching, this study shows that upon extracellular alkalinization, a pool of TRPV5-containing vesicles is rapidly recruited to the cell surface without collapsing into the plasma membrane. These vesicles contain functional TRPV5 channels since extracellular alkalinization is accompanied by increased TRPV5 activity. Conversely, upon subsequent extracellular acidification, vesicles are retrieved from the plasma membrane, simultaneously resulting in decreased TRPV5 activity. Thus, TRPV5 accesses the extracellular compartment via transient openings of vesicles, suggesting that rapid responses of constitutive active TRP channels to physiological stimuli rely on vesicular “kiss and linger” interactions with the plasma membrane.
Mesh Headings (Keywords): Animals, Calcium, Cell Membrane, Dogs, Humans, Hydrogen-Ion Concentration, Protein Transport, Transient Receptor Potential Channels, Transport Vesicles
Check for Full Text / PubMed Unique Identifier (PMID): 17178838
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