PMID- 33007049 OWN - NLM STAT- MEDLINE DCOM- 20201231 LR - 20240429 IS - 1553-7374 (Electronic) IS - 1553-7366 (Print) IS - 1553-7366 (Linking) VI - 16 IP - 10 DP - 2020 Oct TI - Identification and characterisation of serotonin signalling in the potato cyst nematode Globodera pallida reveals new targets for crop protection. PG - e1008884 LID - 10.1371/journal.ppat.1008884 [doi] LID - e1008884 AB - Plant parasitic nematodes are microscopic pathogens that invade plant roots and cause extensive damage to crops. We have used a chemical biology approach to define mechanisms underpinning their parasitic behaviour: We discovered that reserpine, a plant alkaloid that inhibits the vesicular monoamine transporter (VMAT), potently impairs the ability of the potato cyst nematode Globodera pallida to enter the host plant root. We show this is due to an inhibition of serotonergic signalling that is essential for activation of the stylet which is used to access the host root. Prompted by this we identified core molecular components of G. pallida serotonin signalling encompassing the target of reserpine, VMAT; the synthetic enzyme for serotonin, tryptophan hydroxylase; the G protein coupled receptor SER-7 and the serotonin-gated chloride channel MOD-1. We cloned each of these molecular components and confirmed their functional identity by complementation of the corresponding C. elegans mutant thus mapping out serotonergic signalling in G. pallida. Complementary approaches testing the effect of chemical inhibitors of each of these signalling elements on discrete sub-behaviours required for parasitism and root invasion reinforce the critical role of serotonin. Thus, targeting the serotonin signalling pathway presents a promising new route to control plant parasitic nematodes. FAU - Crisford, Anna AU - Crisford A AUID- ORCID: 0000-0001-5775-643X AD - School of Biological Sciences, University of Southampton, Southampton, United Kingdom. FAU - Calahorro, Fernando AU - Calahorro F AUID- ORCID: 0000-0003-0659-7728 AD - School of Biological Sciences, University of Southampton, Southampton, United Kingdom. FAU - Ludlow, Elizabeth AU - Ludlow E AD - School of Biological Sciences, University of Southampton, Southampton, United Kingdom. FAU - Marvin, Jessica M C AU - Marvin JMC AD - Centre for Plant Sciences, School of Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom. FAU - Hibbard, Jennifer K AU - Hibbard JK AD - Centre for Plant Sciences, School of Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom. FAU - Lilley, Catherine J AU - Lilley CJ AD - Centre for Plant Sciences, School of Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom. FAU - Kearn, James AU - Kearn J AD - School of Biological Sciences, University of Southampton, Southampton, United Kingdom. FAU - Keefe, Francesca AU - Keefe F AD - School of Biological Sciences, University of Southampton, Southampton, United Kingdom. FAU - Johnson, Peter AU - Johnson P AUID- ORCID: 0000-0001-7780-8911 AD - School of Biological Sciences, University of Southampton, Southampton, United Kingdom. FAU - Harmer, Rachael AU - Harmer R AD - School of Biological Sciences, University of Southampton, Southampton, United Kingdom. FAU - Urwin, Peter E AU - Urwin PE AUID- ORCID: 0000-0003-0398-2372 AD - Centre for Plant Sciences, School of Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom. FAU - O'Connor, Vincent AU - O'Connor V AD - School of Biological Sciences, University of Southampton, Southampton, United Kingdom. FAU - Holden-Dye, Lindy AU - Holden-Dye L AUID- ORCID: 0000-0002-9704-1217 AD - School of Biological Sciences, University of Southampton, Southampton, United Kingdom. LA - eng GR - P40 OD010440/OD/NIH HHS/United States GR - BB/J006017/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom GR - BB/J006890/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20201002 PL - United States TA - PLoS Pathog JT - PLoS pathogens JID - 101238921 RN - 333DO1RDJY (Serotonin) SB - IM MH - Animals MH - Crop Protection/*methods MH - *Host-Pathogen Interactions MH - Nematoda/*physiology MH - Plant Diseases/*parasitology MH - Serotonin/*metabolism MH - *Signal Transduction MH - Solanum tuberosum/*metabolism/parasitology PMC - PMC7556481 COIS- I have read the journal's policy and the authors of this manuscript have the following competing interests: Holden-Dye, O'Connor and Urwin are inventors for filed UK Patent Application no. 1710057.9 Reserpine Seed Coating; United States Patent Application No. 16/625,580 Reserpine Seed Coating; European Patent Application No. 187337401.2-1110/3641543 Reserpine Seed Coating. EDAT- 2020/10/03 06:00 MHDA- 2021/01/01 06:00 PMCR- 2020/10/02 CRDT- 2020/10/02 17:08 PHST- 2020/04/17 00:00 [received] PHST- 2020/08/14 00:00 [accepted] PHST- 2020/10/14 00:00 [revised] PHST- 2020/10/03 06:00 [pubmed] PHST- 2021/01/01 06:00 [medline] PHST- 2020/10/02 17:08 [entrez] PHST- 2020/10/02 00:00 [pmc-release] AID - PPATHOGENS-D-20-00790 [pii] AID - 10.1371/journal.ppat.1008884 [doi] PST - epublish SO - PLoS Pathog. 2020 Oct 2;16(10):e1008884. doi: 10.1371/journal.ppat.1008884. eCollection 2020 Oct.