TRP channels interaction with lipids and its implications in disease

Abstract

Transient receptor potential (TRP) proteins are a family of ion channels central for sensory signaling. These receptors and, in particular, those involved in thermal sensing are also involved in pain signaling. Noteworthy, thermosensory receptors are polymodal ion channels that respond to both physical and chemical stimuli, thus integrating different environmental clues. In addition, their activity is modulated by algesic agents and lipidergic substances that are primarily released in pathological states. Lipids and lipid-like molecules have been found that can directly activate some thermosensory channels or modulate their activity by either potentiating or inhibiting it. To date, more than 50 endogenous lipids that can regulate TRP channel activity in sensory neurons have been described, thus representing the majority of known endogenous TRP channel modulators. Lipid modulators of TRP channels comprise lipids from a variety of metabolic pathways, including metabolites of the cyclooxygenase, lipoxygenase and cytochrome-P450 pathways, phospholipids and lysophospholipids. Therefore, TRP-channels are able to integrate and interpret incoming signals from the different metabolic lipid pathways. Taken together, the large number of lipids that can activate, sensitize or inhibit neuronal TRP-channels highlights the pivotal role of these molecules in sensory biology as well as in pain transduction and perception. This article is part of a Special Issue entitled: Lipid-protein interactions. Guest Editors: Amitabha Chattopadhyay and Jean-Marie Ruysschaert.

Structure of the Full-Length TRPV2 Channel by Cryo-EM

“…1d). This activity may be intrinsic to TRPV2; however, it remains possible that TRPV2 function is altered in the presence of cellular factors absent from the reconstituted system, such as membrane lipids that modulate channel activity 41 . The absence of cellular factors during cryo-EM data acquisition may also affect the overall full-length TRPV2 architecture in the apo state.…”

“…Heterologously expressed TRPV2 is sensitive to phosphoinositide lipid levels in the membrane 17 . In turn, endogenously expressed endosomal TRPV2 may be modulated by a variety of phosphoinositides, which are abundant in intracellular membranes 14,[39][40][41][42][43] . In addition TRPV2 activity may be regulated by post-translational modifications, as well as changes in channel expression and localization 14 .…”

The Interplay between Cytoskeleton and Calcium Dynamics

“…Within this group we should highlight the transient receptor potential (TRP) ion channel family, a large family of channels involved in sensory perception, smooth muscle contraction-relaxation cycles and cell proliferation [6]. Members of the TRPC (transient receptor potential canonical) family are also involved in the organization of heteromeric Ca 2+ channels that respond to intracellular Ca 2+ store depletion [7].…”

Regulation of thermoTRPs by lipids

“…The roles of arachidonic acid, diacylglycerol and polyunsaturated fatty acids (PUFAs) have been studied extensively and thus, we would like to refer the reader to a recent review on this subject. 6 Thus, here we will specifically discuss how thermoTRPs are regulated by phospholipids, lysophospholipids, monounsaturated fatty acids and cholesterol.…”