Moreno H, Nadal M, Leznik E, Sugimori M, Lax I, Schlessinger J, Llinás R
Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016, USA.
Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14997-5002. doi: 10.1073/pnas.95.25.14997.
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.
酪氨酸磷酸化已被证明是脊椎动物和无脊椎动物突触传递的重要调节因子。这些发现提示存在能够在突触处或其附近激活这种广泛存在的信号机制的细胞外配体。此类配体的例子是肽生长因子，它们在结合后会激活受体酪氨酸激酶。为了深入了解鱿鱼巨大突触中受体酪氨酸激酶激活的生理后果，在此实验准备中测试了一系列生长因子。电生理、药理学和生化分析表明，神经生长因子（NGF）会引发突触后电位幅度的急性特异性降低，而不会影响突触前动作电位的产生或突触前钙电流。NGF的作用靶点位于突触后位点，涉及一种新的类TrkA受体。鱿鱼受体与针对哺乳动物TrkA产生的抗体发生交叉反应，在NGF刺激下会发生酪氨酸磷酸化，并被特定的药理学抑制剂阻断。所描述的这种调节强调了生长因子在无脊椎动物突触传递中的重要作用。
