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5-羟色胺受体调节异源受体复合物中 TrkB 受体的功能。

Serotonin Receptor 5-HT Regulates TrkB Receptor Function in Heteroreceptor Complexes.

机构信息

Cellular Neurophysiology, Center of Physiology, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany.

Laboratory of Behavioral Neurogenomics, Federal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Prospekt Lavrentyeva 10, 630090 Novosibirsk, Russia.

出版信息

Cells. 2022 Aug 2;11(15):2384. doi: 10.3390/cells11152384.

DOI:10.3390/cells11152384
PMID:35954229
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9368268/
Abstract

Serotonin receptor 5-HT and tropomyosin receptor kinase B (TrkB) strongly contribute to neuroplasticity regulation and are implicated in numerous neuronal disorders. Here, we demonstrate a physical interaction between 5-HT and TrkB in vitro and in vivo using co-immunoprecipitation and biophysical and biochemical approaches. Heterodimerization decreased TrkB autophosphorylation, preventing its activation with agonist 7,8-DHF, even with low 5-HT receptor expression. A blockade of 5-HT receptor with the preferential antagonist ketanserin prevented the receptor-mediated downregulation of TrkB phosphorylation without restoring the TrkB response to its agonist 7,8-DHF in vitro. In adult mice, intraperitoneal ketanserin injection increased basal TrkB phosphorylation in the frontal cortex and hippocampus, which is in accordance with our findings demonstrating the prevalence of 5-HT-TrkB heteroreceptor complexes in these brain regions. An expression analysis revealed strong developmental regulation of 5-HT and TrkB expressions in the cortex, hippocampus, and especially the striatum, demonstrating that the balance between TrkB and 5-HT may shift in certain brain regions during postnatal development. Our data reveal the functional role of 5-HT-TrkB receptor heterodimerization and suggest that the regulated expression of 5-HT and TrkB is a molecular mechanism for the brain-region-specific modulation of TrkB functions during development and under pathophysiological conditions.

摘要

血清素受体 5-HT 和原肌球蛋白受体激酶 B（TrkB）强烈参与神经可塑性调节，并与许多神经元疾病有关。在这里，我们使用共免疫沉淀和生物物理及生化方法，在体外和体内证明了 5-HT 和 TrkB 之间的物理相互作用。异二聚化降低了 TrkB 的自身磷酸化，从而阻止其与激动剂 7,8-DHF 激活，即使 5-HT 受体表达较低也是如此。用选择性拮抗剂酮色林阻断 5-HT 受体，可防止受体介导的 TrkB 磷酸化下调，而不会恢复 TrkB 对其激动剂 7,8-DHF 的反应，即使在体外也是如此。在成年小鼠中，腹腔内注射酮色林增加了前额叶皮层和海马体中的基础 TrkB 磷酸化，这与我们的发现一致，即表明 5-HT-TrkB 异源受体复合物在这些脑区中普遍存在。表达分析显示，5-HT 和 TrkB 在皮层、海马体，特别是纹状体中的表达具有强烈的发育调控，表明在出生后发育过程中，TrkB 和 5-HT 之间的平衡可能会在某些脑区发生变化。我们的数据揭示了 5-HT-TrkB 受体异二聚化的功能作用，并表明 5-HT 和 TrkB 的调节表达是在发育过程中和在病理生理条件下，对 TrkB 功能进行脑区特异性调节的分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/9368268/d9f8aa272de9/cells-11-02384-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/9368268/00c869d90645/cells-11-02384-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/9368268/2844668474ea/cells-11-02384-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/9368268/412f45d92c35/cells-11-02384-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/9368268/647c18f2fb57/cells-11-02384-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/9368268/0f9bd025a3e7/cells-11-02384-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/9368268/d9f8aa272de9/cells-11-02384-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/9368268/00c869d90645/cells-11-02384-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/9368268/2844668474ea/cells-11-02384-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/9368268/412f45d92c35/cells-11-02384-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/9368268/647c18f2fb57/cells-11-02384-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/9368268/0f9bd025a3e7/cells-11-02384-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d806/9368268/d9f8aa272de9/cells-11-02384-g006.jpg

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