The Role of Membrane Lipids in Light-Activation of Drosophila TRP Channels.

Elisheva Rhodes-Mordov,Rachel Zaguri,Tal Brandwine-Shemmer,Rita Gutorov,Baruch Minke,Ben Katz

doi:10.3390/biom12030382

Abstract

Transient Receptor Potential (TRP) channels constitute a large superfamily of polymodal channel proteins with diverse roles in many physiological and sensory systems that function both as ionotropic and metabotropic receptors. From the early days of TRP channel discovery, membrane lipids were suggested to play a fundamental role in channel activation and regulation. A prominent example is the Drosophila TRP and TRP-like (TRPL) channels, which are predominantly expressed in the visual system of Drosophila. Light activation of the TRP and TRPL channels, the founding members of the TRP channel superfamily, requires activation of phospholipase Cβ (PLC), which hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) into Diacylglycerol (DAG) and Inositol 1, 4,5-trisphosphate (IP3). However, the events required for channel gating downstream of PLC activation are still under debate and led to several hypotheses regarding the mechanisms by which lipids gate the channels. Despite many efforts, compelling evidence of the involvement of DAG accumulation, PIP2 depletion or IP3-mediated Ca2+ release in light activation of the TRP/TRPL channels are still lacking. Exogeneous application of poly unsaturated fatty acids (PUFAs), a product of DAG hydrolysis was demonstrated as an efficient way to activate the Drosophila TRP/TRPL channels. However, compelling evidence for the involvement of PUFAs in physiological light-activation of the TRP/TRPL channels is still lacking. Light-induced mechanical force generation was measured in photoreceptor cells prior to channel opening. This mechanical force depends on PLC activity, suggesting that the enzymatic activity of PLC converting PIP2 into DAG generates membrane tension, leading to mechanical gating of the channels. In this review, we will present the roles of membrane lipids in light activation of Drosophila TRP channels and present the many advantages of this model system in the exploration of TRP channel activation under physiological conditions.

Highlights

The Transient Receptor Potential (TRP) superfamily, which is conserved through evolution, consists of seven subfamilies (TRPC, TRPV, TRPM, TRPA, TRPN, TRPML, and TRPP) and its members are expressed in many cell types, including excitable as well as nonexcitable cells [1]
TRPC channels can be activated by exogeneous application of DAG together with the Despite many efforts of over the years,TRPC
Drosophila retina is a highly valued mammalian TRPC channels that contains a TRP-enriched tissue combined with the power preparation for investigating the roles of TRP/TRPL channels under physiological conof the Drosophila molecular genetics and the accuracy of light activation

Summary

Introduction

The Transient Receptor Potential (TRP) superfamily, which is conserved through evolution, consists of seven subfamilies (TRPC, TRPV, TRPM, TRPA, TRPN, TRPML, and TRPP) and its members are expressed in many cell types, including excitable as well as nonexcitable cells [1]. The measured force generated by changes in membrane lipid packing and the generation of membrane tension during the enzymatic activity of PLC and the conversion of PIP2 into DAG, gate the mechanical sensitive TRP/TRPL channels. This theory emphasizes that the lipid environment in which the channels are embedded is crucial for their performance. We will discuss conflicting and missing data required for elucidating the mechanism underlying lipid-activation of the TRP/TRPL channels

The Involvement of the Inositol-Lipid Signaling in TRP Channel Activation

PLCβ incomplex a still with unclear way activates thewhich

Lipid of the Drosophila

Evidence for Lipids Action as Second Messengers

PUFAs Activation of TRP and TRPL Channels in the Dark

Lipid Rafts and Modulation of TRPL Channel Activity by Cholesterol

Concluding