Unveiling TRPV1 spatio-temporal organization in live cell membranes

• Published in: PloS one Vol. 10; no. 3; p. e0116900
• Main Authors: Storti, Barbara, Di Rienzo, Carmine, Cardarelli, Francesco, Bizzarri, Ranieri, Beltram, Fabio
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.03.2015; Public Library of Science (PLoS)
• Subjects: Animals; Capsaicin receptors; Caveolin; Caveolin 1 - metabolism; Caveolin-1; Cell Membrane - metabolism; Cell membranes; CHO Cells; Cholesterol; Cricetulus; Cytoskeleton; Desensitization; Endocytosis; Energy transfer; Experiments; Fluorescence; Fluorescence resonance energy transfer; Fluorescence Resonance Energy Transfer - methods; Localization; Membranes; Microscopy; Microtubules; Microtubules - metabolism; Nanotechnology; Pain perception; Proteins; Selective binding; Spectrum analysis; Transient receptor potential proteins; TRPV Cation Channels - metabolism; Variation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0116900

Transient Receptor Potential Vanilloid 1 (TRPV1) is a non-selective cation channel that integrates several stimuli into nociception and neurogenic inflammation. Here we investigated the subtle TRPV1 interplay with candidate membrane partners in live cells by a combination of spatio-temporal fluctuation techniques and fluorescence resonance energy transfer (FRET) imaging. We show that TRPV1 is split into three populations with fairly different molecular properties: one binding to caveolin-1 and confined into caveolar structures, one actively guided by microtubules through selective binding, and one which diffuses freely and is not directly implicated in regulating receptor functionality. The emergence of caveolin-1 as a new interactor of TRPV1 evokes caveolar endocytosis as the main desensitization pathway of TRPV1 receptor, while microtubule binding agrees with previous data suggesting the receptor stabilization in functional form by these cytoskeletal components. Our results shed light on the hitherto unknown relationships between spatial organization and TRPV1 function in live-cell membranes.