Transactivation of TrkB Receptors by Oxytocin and Its G Protein-Coupled Receptor.

Autor:	Mitre M; Departments of Cell Biology, Neuroscience & Physiology, and Psychiatry, Skirball Institute for Biomolecular Medicine, New York, NY, United States.; Neuroscience Institute, New York University Langone Medical Center, New York, NY, United States.; Departments of Cell Biology, Psychiatry, New York University Langone Medical Center, New York, NY, United States.; Department of Neuroscience and Physiology, New York University Langone Medical Center, New York, NY, United States.; Department of Otolaryngology, New York University Langone Medical Center, New York, NY, United States.; Center for Neural Science, New York University, New York, NY, United States., Saadipour K; Departments of Cell Biology, Neuroscience & Physiology, and Psychiatry, Skirball Institute for Biomolecular Medicine, New York, NY, United States., Williams K; Departments of Biology and Psychology, University of Georgia, Athens, GA, United States., Khatri L; Departments of Cell Biology, Neuroscience & Physiology, and Psychiatry, Skirball Institute for Biomolecular Medicine, New York, NY, United States., Froemke RC; Departments of Cell Biology, Neuroscience & Physiology, and Psychiatry, Skirball Institute for Biomolecular Medicine, New York, NY, United States.; Neuroscience Institute, New York University Langone Medical Center, New York, NY, United States.; Department of Neuroscience and Physiology, New York University Langone Medical Center, New York, NY, United States.; Department of Otolaryngology, New York University Langone Medical Center, New York, NY, United States.; Center for Neural Science, New York University, New York, NY, United States., Chao MV; Departments of Cell Biology, Neuroscience & Physiology, and Psychiatry, Skirball Institute for Biomolecular Medicine, New York, NY, United States.; Neuroscience Institute, New York University Langone Medical Center, New York, NY, United States.; Departments of Cell Biology, Psychiatry, New York University Langone Medical Center, New York, NY, United States.; Department of Neuroscience and Physiology, New York University Langone Medical Center, New York, NY, United States.; Center for Neural Science, New York University, New York, NY, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in molecular neuroscience [Front Mol Neurosci] 2022 Jun 02; Vol. 15, pp. 891537. Date of Electronic Publication: 2022 Jun 02 (Print Publication: 2022).
DOI:	10.3389/fnmol.2022.891537
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Mitre, Saadipour, Williams, Khatri, Froemke and Chao.)
Databáze:	MEDLINE
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