Abstract

Transient receptor potential (TRP) or transient receptor potential channels are a highly diverse family of mostly non-selective cation channels. In the mammalian genome, 28 members can be identified, most of them being expressed predominantly in the plasma membrane with the exception of the mucolipins or TRPMLs which are expressed in the endo-lysosomal system. In mammalian organisms, TRPMLs have been associated with a number of critical endo-lysosomal functions such as autophagy, endo-lysosomal fusion/fission and trafficking, lysosomal exocytosis, pH regulation, or lysosomal motility and positioning. The related non-selective two-pore cation channels (TPCs), likewise expressed in endosomes and lysosomes, have also been found to be associated with endo-lysosomal trafficking, autophagy, pH regulation, or lysosomal exocytosis, raising the question why these two channel families have evolved independently. We followed TRP/TRPML channels and TPCs through evolution and describe here in which species TRP/TRPMLs and/or TPCs are found, which functions they have in different species, and how this compares to the functions of mammalian orthologs.

Highlights

  • The earliest evidence for life on Earth dates back some 3.5 billion years [1]

  • All three TRPMLs are activated by the phosphoinositide PI(3,5)P2, a major constituent of endo-lysosomal membranes, and by the luminal pH/proton concentration which differs between various endosomal organelles and lysosomes [27,32,39]

  • More than 80% of the putative Transient receptor potential (TRP) channels in algae and unicellular organisms appear to originate in TRPP/TRPML clusters, in agreement with TRPP and TRPV channels found in the protist Thecamonas trahens [2,53]

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Summary

Introduction

The earliest evidence for life on Earth dates back some 3.5 billion years [1]. First, prokaryotes (bacteria and archaea) and certain eukaryotes (protozoa, algae, and fungi) evolved, gradually plants and animals started developing (their evolution started about 5–25 million years ago). The founding member of the TRP family was initially discovered as a receptor-operated sensory cation channel in a blind strain of Drosophila melanogaster [6,7,8], which paved the way for the discovery of the canonical (TRPC1–TRPC7) subfamily of mammalian TRPs [9,10]. Beyond the TRPC channels, the other 21 members of the mammalian TRP family can be grouped in five branches, based on sequence homology: vanilloid (TRPV1-TRPV6), melastatin (TRPM1-8), ankyrin (TRPA1), mucolipin (TRPML1-3), and polycystin (TRPP1-3). An alternative classification of TRP channels proposed by Zang et al (2018) combines its physiological function with endogenous activation mechanisms, leading to three subgroups: metabotropic, sensory, and organellar TRPs. Thereby, a functional subgroup can contain members from different subfamilies, important when comparing TRP channels from different species. Fundamental physiological and cellular functions of TRP channels may be the reason for them being highly conserved in yeast and mammals. We discuss evolutionary aspects of organellar TRP channels, in particular the TRPML/MCOLN channels, and the functionally related two-pore channels (TPCs)

TRPMLs—More and More over Time
TRPMLs—Evolutionary Beginnings
TRPs in Fungi and Plants—Barely Present
TPCs in Metazoa
Findings
Summary
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