Transactivation of TrkB Receptors by Oxytocin and Its G Protein-Coupled Receptor.
Transactivation of TrkB Receptors by Oxytocin and Its G Protein-Coupled Receptor.
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DOI：
10.3389/fnmol.2022.891537
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发表时间：
2022
影响因子：
4.8
通讯作者：
Chao, Moses V.
中科院分区：
文献类型：
--
作者：
Mitre, Mariela;Saadipour, Khalil;Williams, Kevin;Khatri, Latika;Froemke, Robert C.;Chao, Moses V.
脑源性神经营养因子（BDNF）与TrkB酪氨酸激酶受体结合，其决定神经元对BDNF的敏感性。TrkB的一个独特特征是能够在称为反式激活的过程中被小分子激活。在这里，我们报告说，脑神经肽催产素增加BDNF TrkB活性在初级皮层神经元和哺乳动物的新皮层在出生后的发展。催产素通过G蛋白偶联受体（GPCR）产生其作用，然而，解释其作用的受体信号事件尚未完全确定。我们发现催产素迅速反式激活TrkB受体在浴应用急性脑切片的2周龄小鼠和在原代皮层培养增加TrkB受体酪氨酸磷酸化。催产素信号的作用可以与相关的加压素受体区分开来。催产素对TrkB受体的反式激活增强了桥蛋白的聚集，桥蛋白是一种负责协调抑制反应的支架蛋白。由于催产素在母亲护理、认知和社会依恋方面表现出亲社会功能，因此它目前是自闭症谱系障碍治疗策略的焦点。有趣的是，催产素和BDNF都与抑郁症、精神分裂症、焦虑和认知的病理生理学有关。这些结果表明，催产素可能依赖于与BDNF信号的串扰，以促进其通过受体反式激活的行动。
Brain-derived Neurotrophic Factor (BDNF) binds to the TrkB tyrosine kinase receptor, which dictates the sensitivity of neurons to BDNF. A unique feature of TrkB is the ability to be activated by small molecules in a process called transactivation. Here we report that the brain neuropeptide oxytocin increases BDNF TrkB activity in primary cortical neurons and in the mammalian neocortex during postnatal development. Oxytocin produces its effects through a G protein-coupled receptor (GPCR), however, the receptor signaling events that account for its actions have not been fully defined. We find oxytocin rapidly transactivates TrkB receptors in bath application of acute brain slices of 2-week-old mice and in primary cortical culture by increasing TrkB receptor tyrosine phosphorylation. The effects of oxytocin signaling could be distinguished from the related vasopressin receptor. The transactivation of TrkB receptors by oxytocin enhances the clustering of gephyrin, a scaffold protein responsible to coordinate inhibitory responses. Because oxytocin displays pro-social functions in maternal care, cognition, and social attachment, it is currently a focus of therapeutic strategies in autism spectrum disorders. Interestingly, oxytocin and BDNF are both implicated in the pathophysiology of depression, schizophrenia, anxiety, and cognition. These results imply that oxytocin may rely upon crosstalk with BDNF signaling to facilitate its actions through receptor transactivation.
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DOI：
10.1073/pnas.0709102105
发表时间：
2008-03-25
影响因子：
11.1
作者：
Jeanneteau, Freddy;Garabedian, Michael J.;Chao, Moses V.
通讯作者：
Chao, Moses V.
影响因子：
16.2
作者：
Huang, Yang Z.;Pan, Enhui;McNamara, James O.
通讯作者：
McNamara, James O.
影响因子：
4.1
作者：
Chatterjee, Oishi;Patil, Krutika;Prasad, T. S. Keshava
通讯作者：
Prasad, T. S. Keshava
影响因子：
8.2
作者：
Cornejo, Maria P.;Mustafa, Emilio R.;Perello, Mario
通讯作者：
Perello, Mario
DOI：
10.1523/jneurosci.5060-08.2009
发表时间：
2009-01-21
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Carim-Todd L;Bath KG;Fulgenzi G;Yanpallewar S;Jing D;Barrick CA;Becker J;Buckley H;Dorsey SG;Lee FS;Tessarollo L
通讯作者：
Tessarollo L