Abstract
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.
Highlights
The Transient Potential Vanilloid 1 or Transient Receptor Potential Vanilloid 1 (TRPV1) belongs to that fascinating class of polymodal membrane receptors that integrate several physical and molecular stimuli and convert them into efficient intracellular signaling [1]
Our findings show that membrane TRPV1 is split, at least, in three pools with distinct functional roles, namely: 1) TRPV1-C, which is trapped in caveolae and likely governs receptor long-term desensitization upon activation, 2) TRPV1T, which is organized in large sub-micron membrane domains whose diffusion is modulated by microtubules and oversees the subtle feedback interaction between receptor and microtubules [10], and 3) TRPV1-I that diffuses on the membrane in a fast and isotropic fashion and might represent a reservoir of the receptor
We investigated whether TRPV1 and caveolin-1 directly interact with each other on the plasma membrane
Summary
The Transient Potential Vanilloid 1 or TRPV1 belongs to that fascinating class of polymodal membrane receptors that integrate several physical and molecular stimuli and convert them into efficient intracellular signaling [1]. TRPV1 is a member of the transient receptor potential (TRP) channel family, which is typified by a predicted six transmembrane domain with intracellular N- and C-termini and a relatively-conserved pore domain [5,6]. TRPV1 is primarily expressed in sensory neurons, where it is involved in pain signaling [7]. This receptor is primarily studied to promote the design of drugs capable of controlling pain stress in humans [8]
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