Faculty Collaboration Database

Use the force, fluke: Ligand-independent gating of Schistosoma mansoni ion channel TRPM_PZQ. Int J Parasitol 2023 Jan 04

Date

01/08/2023

Pubmed ID

36610555

DOI

10.1016/j.ijpara.2022.11.004

Scopus ID

2-s2.0-85146298174 (requires institutional sign-in at Scopus site)

Abstract

The parasitic flatworm ion channel, TRPM_PZQ, is a non-selective cation channel that mediates Ca²⁺ entry and membrane depolarization when activated by the anthelmintic drug, praziquantel (PZQ). TRPM_PZQ is conserved in all platyhelminth genomes scrutinized to date, with the sensitivity of TRPM_PZQ in any particular flatworm correlating with the overall sensitivity of the worm to PZQ. Conservation of this channel suggests it plays a role in flatworm physiology, but the nature of the endogenous cues that activate this channel are currently unknown. Here, we demonstrate that TRPM_PZQ is activated in a ligand-independent manner by membrane stretch, with the electrophysiological signature of channel opening events being identical whether evoked by negative pressure, or by PZQ. TRPM_PZQ is therefore a multimodal ion channel gated by both physical and chemical cues. The mechanosensitivity of TRPM_PZQ is one route for endogenous activation of this ion channel that holds relevance for schistosome physiology given the persistent pressures and mechanical cues experienced throughout the parasite life cycle.

Author List

Chulkov EG, Isaeva E, Stucky CL, Marchant JS

Authors

Olena Isaeva PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Cheryl L. Stucky PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin