A small molecule screen identifies novel inhibitors of mechanosensory nematocyst discharge in Hydra

Diana Hofmann,Suat Özbek,Bruno Gideon Bergheim,Simone Grässle,Stefan Bräse,Niharika Garg,Sylvia Vanderheiden,Nicole Jung

doi:10.1038/s41598-021-99974-7

Diana Hofmann, Suat Özbek + Show 6 more

Open Access

https://doi.org/10.1038/s41598-021-99974-7

Copy DOI

Abstract

Cnidarians are characterized by the possession of stinging organelles, called nematocysts, which they use for prey capture and defense. Nematocyst discharge is controlled by a mechanosensory apparatus with analogies to vertebrate hair cells. Members of the transient receptor potential (TRPN) ion channel family are supposed to be involved in the transduction of the mechanical stimulus. A small molecule screen was performed to identify compounds that affect nematocyst discharge in Hydra. We identified several [2.2]paracyclophanes that cause inhibition of nematocyst discharge in the low micro-molar range. Further structure–activity analyses within the compound class of [2.2]paracyclophanes showed common features that are required for the inhibitory activity of the [2.2]paracyclophane core motif. This study demonstrates that Hydra can serve as a model for small molecule screens targeting the mechanosensory apparatus in native tissues.

Highlights

Cnidarians are characterized by the possession of stinging organelles, called nematocysts, which they use for prey capture and defense
Prey capture was scored after 10 min by recording the ratio of animals showing a reduced killing of prey as compared to control animals incubated in Hydra medium (HM)
We carried out a small molecule screen to identify compounds that affect nematocyst discharge in Hydra

Summary

Introduction

Cnidarians are characterized by the possession of stinging organelles, called nematocysts, which they use for prey capture and defense. The superfamily of transient receptor potential (TRP) proteins, which comprises seven subfamilies (TRPA, TRPC, TRPM, TRPML, TRPN, TRPP, and TRPV), are non-selective ion channels enabling animals to sense a variety of environmental stimuli, such as light, odors, temperature, and mechanical forces[9,10,11,12]. Their molecular architecture is characterized by six transmembrane domains and, in most subfamilies, the possession of N-terminal ankyrin repeats arranged in a tandem array. Analyses of TRPN channels in native tissues are still hampered by a lack of specific pharmacological tools

Objectives

Methods

Results

Conclusion