Postsynaptic expression of an epidermal growth factor receptor regulates cholinergic synapse formation between identified molluscan neurons.
Epidermal growth factor (EGF) family members are conserved in both vertebrates and invertebrates. Recent studies suggest that EGF ligands in invertebrates may have neurotrophic actions that possibly compensate for the apparent absence of neurotrophins in these species. In this study, we have cloned an EGF receptor from the mollusk Lymnaea stagnalis (L-EGFR), and shown that L-EGFR is the receptor for a previously identified EGF-like peptide in Lymnaea, named Lymnaea EGF (L-EGF). Knock-down of L-EGFR expression prevented L-EGF-induced excitatory synapse formation between identified cholinergic neuron visceral dorsal 4 (VD4) and its postsynaptic partner left pedal dorsal 1 (LPeD1). Moreover, knock-down of L-EGFR also prevented synapse formation induced by Lymnaea brain conditioned medium, suggesting that L-EGF is the most important, if not the only, brain-derived factor that promotes excitatory cholinergic synapse formation in Lymnaea. Thus, our data establish canonical EGF/EGFR signaling as an important synaptotrophic mechanism in invertebrates.
van Kesteren
Ronald E
RE
Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, De Boelelaan 1085, 1081HV Amsterdam, The Netherlands. ronald.van.kesteren@cncr.vu.nl
Gagatek
Jessica S
JS
Hagendorf
Antje
A
Gouwenberg
Yvonne
Y
Smit
August B
AB
Syed
Naweed I
NI
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006801:Humans; D017403:In Situ Hybridization; D008195:Lymnaea / Q000502:physiology*; D009414:Nerve Growth Factors / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D013569:Synapses / Q000378:metabolism*
D009414:Nerve Growth Factors; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D000109:Acetylcholine