Nerve growth factor acutely reduces chemical transmission by means of postsynaptic TrkA-like receptors in squid giant synapse

Tyrosine phosphorylation has been shown to be an important modulator of syn aptic transmission in both vertebrates and invertebrates. Such findings hin t toward the existence of extracellular ligands capable of activating this widely represented signaling mechanism at or close to the synapse. Examples of such ligands are the peptide growth factors which, on binding. activate receptor tyrosine kinases. To gain insight into the physiological conseque nces of receptor tyrosine kinase activation in squid giant synapse, a serie s of growth factors was tested in this preparation. Electrophysiological, p harmacological, and biochemical analysis demonstrated that nerve growth fac tor (NGF) triggers an acute and specific reduction of the postsynaptic pote ntial amplitude, without affecting the presynaptic spike generation or pres ynaptic calcium current. The NGF target is localized at a postsynaptic site and involves a new TrkA-like receptor. The squid receptor crossreacts with antibodies generated against mammalian TrkA, is tyrosine phosphorylated in response to NGF stimulation, and is blocked by specific pharmacological in hibitors. The modulation described emphasizes the important role of growth factors on invertebrate synaptic transmission.