Department of Cellular Neurophysiology, Hannover Medical School, Hannover 30625, Germany.
Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia.
J Cell Sci. 2021 Feb 19;134(4):jcs249193. doi: 10.1242/jcs.249193.
Morphological remodeling of dendritic spines is critically involved in memory formation and depends on adhesion molecules. Serotonin receptors are also implicated in this remodeling, though the underlying mechanisms remain enigmatic. Here, we uncovered a signaling pathway involving the adhesion molecule L1CAM (L1) and serotonin receptor 5-HT (5-HTR, encoded by ). Using Förster resonance energy transfer (FRET) imaging, we demonstrated a physical interaction between 5-HTR and L1, and found that 5-HTR-L1 heterodimerization facilitates mitogen-activated protein kinase activation in a G-dependent manner. We also found that 5-HTR-L1-mediated signaling is involved in G-dependent modulation of cofilin-1 activity. In hippocampal neurons , the 5-HTR-L1 pathway triggers maturation of dendritic spines. Thus, the 5-HTR-L1 signaling module represents a previously unknown molecular pathway regulating synaptic remodeling.
树突棘形态重塑在记忆形成中起着关键作用，并且依赖于黏附分子。血清素受体也与这种重塑有关，尽管其潜在机制仍不清楚。在这里，我们揭示了一个涉及黏附分子 L1CAM（L1）和血清素受体 5-HT（5-HTR，由 编码）的信号通路。使用Förster 共振能量转移（FRET）成像，我们证明了 5-HTR 和 L1 之间存在物理相互作用，并发现 5-HTR-L1 异二聚体化以 G 依赖性方式促进有丝分裂原活化蛋白激酶的激活。我们还发现，5-HTR-L1 介导的信号转导参与了 G 依赖性调节胞衬蛋白-1 活性。在海马神经元中，5-HTR-L1 途径触发树突棘的成熟。因此，5-HTR-L1 信号模块代表了一个以前未知的分子途径，调节突触重塑。
