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 synaptic transmission in both vertebrates and invertebrates. Such findings hint 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 consequences of receptor tyrosine kinase activation in squid giant synapse, a series of growth factors was tested in this preparation. Electrophysiological, pharmacological, and biochemical analysis demonstrated that nerve growth factor (NGF) triggers an acute and specific reduction of the postsynaptic potential amplitude, without affecting the presynaptic spike generation or presynaptic 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 inhibitors. The modulation described emphasizes the important role of growth factors on invertebrate synaptic transmission.

酪氨酸磷酸化（Tyrosine phosphorylation）已被证实是脊椎动物与无脊椎动物突触传递的关键调控因子。该研究发现提示，存在可在突触处或突触邻近区域激活这一广泛分布的信号转导通路的细胞外配体。此类配体的典型代表为肽类生长因子，其通过与受体结合激活受体酪氨酸激酶（receptor tyrosine kinase）。为探究鱿鱼巨突触中受体酪氨酸激酶激活的生理效应，研究人员对该实验标本中的一系列生长因子展开了检测。电生理、药理学及生化分析结果显示，神经生长因子（nerve growth factor, NGF）可引发突触后电位幅度出现急性且特异性的降低，且不会影响突触前动作电位的产生或突触前钙电流。NGF的作用靶点定位于突触后位点，并涉及一种新型类TrkA受体。该鱿鱼受体可与针对哺乳动物TrkA制备的抗体发生交叉反应，在接受NGF刺激时会发生酪氨酸磷酸化，且可被特异性药理学抑制剂阻断。本研究揭示的调控效应凸显了生长因子在无脊椎动物突触传递中的重要功能。