A Small Molecule Screen Identifies Novel Inhibitors of Mechanosensory Nematocyst Discharge in Hydra

Overview

Journal Sci Rep

Specialty Science

Date 2021 Oct 19

PMID 34663887

Citations 1

Authors

Diana Hofmann

Niharika Garg

Simone Grassle

Sylvia Vanderheiden

Bruno Gideon Bergheim

Stefan Brase

Nicole Jung

Suat Ozbek

Affiliations

Soon will be listed here.

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.

Citing Articles

Piezo proteins, mechano reception and behaviour in Hydra.

Alzugaray M, Gavazzi M, Griffo L, Ronderos J Sci Rep. 2025; 15(1):6440.

PMID: 39987331 PMC: 11846868. DOI: 10.1038/s41598-025-91048-2.

Linking Research Data with Physically Preserved Research Materials in Chemistry.

Lin C, Huang P, Grassle S, Grathwol C, Tremouilhac P, Vanderheiden S Sci Data. 2025; 12(1):130.

PMID: 39843501 PMC: 11754846. DOI: 10.1038/s41597-025-04404-2.

A predatory gastrula leads to symbiosis-independent settlement in Aiptasia.

Maegele I, Rupp S, Ozbek S, Guse A, Hambleton E, Holstein T Proc Natl Acad Sci U S A. 2023; 120(40):e2311872120.

PMID: 37748072 PMC: 10556626. DOI: 10.1073/pnas.2311872120.

References

Zhang W, Cheng L, Kittelmann M, Li J, Petkovic M, Cheng T . Ankyrin Repeats Convey Force to Gate the NOMPC Mechanotransduction Channel. Cell. 2015; 162(6):1391-403. PMC: 4568062. DOI: 10.1016/j.cell.2015.08.024. View

Friedmann C, Ay S, Brase S . Improved synthesis of enantiopure 4-hydroxy[2.2]paracyclophane. J Org Chem. 2010; 75(13):4612-4. DOI: 10.1021/jo100468s. View

W, Hessinger . ANTAGONISTIC FREQUENCY TUNING OF HAIR BUNDLES BY DIFFERENT CHEMORECEPTORS REGULATES NEMATOCYST DISCHARGE. J Exp Biol. 1994; 187(1):57-73. DOI: 10.1242/jeb.187.1.57. View

Liman E, Corey D, Dulac C . TRP2: a candidate transduction channel for mammalian pheromone sensory signaling. Proc Natl Acad Sci U S A. 1999; 96(10):5791-6. PMC: 21939. DOI: 10.1073/pnas.96.10.5791. View

Watson G, Hessinger D . Receptors for N-acetylated sugars may stimulate adenylate cyclase to sensitize and tune mechanoreceptors involved in triggering nematocyst discharge. Exp Cell Res. 1992; 198(1):8-16. DOI: 10.1016/0014-4827(92)90142-u. View

Gillespie P, Walker R . Molecular basis of mechanosensory transduction. Nature. 2001; 413(6852):194-202. DOI: 10.1038/35093011. View

Caterina M, Schumacher M, Tominaga M, Rosen T, Levine J, Julius D . The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature. 1997; 389(6653):816-24. DOI: 10.1038/39807. View

Zheng W, Holt J . The Mechanosensory Transduction Machinery in Inner Ear Hair Cells. Annu Rev Biophys. 2020; 50:31-51. PMC: 8163026. DOI: 10.1146/annurev-biophys-062420-081842. View

Zanini D, Gopfert M . Mechanosensation: tethered ion channels. Curr Biol. 2013; 23(9):R349-51. DOI: 10.1016/j.cub.2013.03.045. View

10.

Beckmann A, Ozbek S . The nematocyst: a molecular map of the cnidarian stinging organelle. Int J Dev Biol. 2012; 56(6-8):577-82. DOI: 10.1387/ijdb.113472ab. View

11.

Ozbek S, Balasubramanian P, Holstein T . Cnidocyst structure and the biomechanics of discharge. Toxicon. 2009; 54(8):1038-45. DOI: 10.1016/j.toxicon.2009.03.006. View

12.

Bestgen S, Seidl C, Wiesner T, Zimmer A, Falk M, Koberle B . Double-Strand DNA Breaks Induced by Paracyclophane Gold(I) Complexes. Chemistry. 2017; 23(26):6315-6322. DOI: 10.1002/chem.201605237. View

13.

Nilius B, Owsianik G . The transient receptor potential family of ion channels. Genome Biol. 2011; 12(3):218. PMC: 3129667. DOI: 10.1186/gb-2011-12-3-218. View

14.

Montell C, Rubin G . Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction. Neuron. 1989; 2(4):1313-23. DOI: 10.1016/0896-6273(89)90069-x. View

15.

Hassan Z, Spuling E, Knoll D, Lahann J, Brase S . Planar chiral [2.2]paracyclophanes: from synthetic curiosity to applications in asymmetric synthesis and materials. Chem Soc Rev. 2018; 47(18):6947-6963. DOI: 10.1039/c7cs00803a. View

16.

Howard J, Bechstedt S . Hypothesis: a helix of ankyrin repeats of the NOMPC-TRP ion channel is the gating spring of mechanoreceptors. Curr Biol. 2004; 14(6):R224-6. DOI: 10.1016/j.cub.2004.02.050. View

17.

Schuler A, Schmitz G, Reft A, Ozbek S, Thurm U, Bornberg-Bauer E . The Rise and Fall of TRP-N, an Ancient Family of Mechanogated Ion Channels, in Metazoa. Genome Biol Evol. 2015; 7(6):1713-27. PMC: 4494053. DOI: 10.1093/gbe/evv091. View

18.

Yan Z, Zhang W, He Y, Gorczyca D, Xiang Y, Cheng L . Drosophila NOMPC is a mechanotransduction channel subunit for gentle-touch sensation. Nature. 2012; 493(7431):221-5. PMC: 3917554. DOI: 10.1038/nature11685. View

19.

Nuchter T, Benoit M, Engel U, Ozbek S, Holstein T . Nanosecond-scale kinetics of nematocyst discharge. Curr Biol. 2006; 16(9):R316-8. DOI: 10.1016/j.cub.2006.03.089. View

20.

Hufnagel L, Kass-Simon G, Lyon M . Functional organization of battery cell complexes in tentacles of Hydra attenuata. J Morphol. 2018; 184(3):323-341. DOI: 10.1002/jmor.1051840307. View