Placozoa and the evolution of monoamine neurotransmitters

COS Seminar
May 19, 2026

Gáspár Jékely

Centre for Organismal Studies, Heidelberg University

@jekely@biologists.social

Evolution of nervous systems

mollusk

Kilias, 1985

planarian

Kellogg, 1903

vertebrate

Jefferys, 1763

Marine animal models

Nematostella
Hydra
Macrostomum
Platynereis
Trichoplax

Neuronal signalling substances are released by vesicle fusion

Basic Neurochemistry: Molecular, Cellular and Medical Aspects

  • vesicular release (at the synapse or neuroendocrine)
  • small-transmitter release (Glu, GABA, ACh, Gly)
  • synaptic or extrasynaptic release of neuropeptides
  • synaptic or extrasynaptic release of monoamines (serotonin, melatonin, noradrenaline etc.)

Monoamines

  • noradrenaline/norepinephrine (fight-or-flight response, arousal, alertness, locus coeruleus of brainstem)
  • serotonin (mood, cognition, reward, learning, memory Raphe nuclei of brainstem)
  • melatonin (the hormone of darkness, pineal gland)
  • octopamine, tyramine (in invertebrates)

Noradrenaline Serotonin Melatonin

A bilaterian innovation?


Biosynthesis of monoamines

  • AADC – aromatic L-amino acid decarboxylase
  • AANAT – aralkylamine N-acetyltransferase (‘timezyme’)
  • HIOMT – Hydroxyindole O-methyltransferase

Signalling via G-protein coupled receptors

Placozoans

Pawel Burkhardt


The GPCR universe

GPCR phylogeny – placozoan orthologs of human melatonin receptors

MS analysis – endogenous placozoan monoamines

Phenethylamine ✓, Tryptamine ✓, Tyramine ✓

Biosynthesis of monoamines

  • AADC – aromatic L-amino acid decarboxylase
  • AANAT – aralkylamine N-acetyltransferase (‘timezyme’)
  • HIOMT – Hydroxyindole O-methyltransferase

A functional AADC enzyme in placozoans

Large-scale pharmacological screen



  • in vitro assay
  • GPCR expressed with promiscuous G-protein
  • compounds added
  • Ca2+ signal measured with reporter

Placozoan monoamine receptors

Receptor expression mapped to cell types

Behavioural effects

Monoamines in placozoans


  • endogenously produced monoamines
  • functional AADC enzyme in fibre cells
  • specific receptors in peptidergic cells
  • non-acetylated monoamines likely endogenous ligands (tyramine, tryptamine, phenethylamine)
  • behavioural effects of agonists

Biosynthesis of monoamines

Human evolutionary pharmacology

  • acetylated versions of the placozoan agonists activate human melatonin receptors
  • hMelB: N-acetyltryptamine as potent as melatonin

Evolution by pathway accretion

Summary


  • common ancestor had non-acetylated versions of monoamines
  • pathway evolved in vertebrates by AANAT neofunctionalisation (Falcón et al 2013)
  • studying placozoans can reveal new human biology
  • melatonin signalling likely vertebrate innovation

Acknowledgements

  • Alexandra Kerbl
  • Karel Mocaer
  • Sanja Jasek
  • David Hug
  • Jules Duruz
  • Mateusz Kostecki
  • Benedikt Dürr
  • Kata Szabó
  • Marzia Matejcek
  • Ana Verbanac
  • Emily Savage
  • Simone Wolters
  • Anja Ciprianidis
  • Kevin Urbansky

Alumni

  • Kei Jokura (NIBB, Okazaki)
  • Luis Bezares (LBDV, Villefranche-sur-mer)
  • Luis Yanez-Guerra (Southampton)
  • Emelie Brodrick (Sussex)
  • Csaba Verasztó (EPFL)

Facilities

  • Réza Shahidi
  • Charlotta Funaya
  • Ulrike Engel