What is it about?

The article "Endolysosomal TPCs regulate social behavior by controlling oxytocin secretion" investigated the relationship between an intracellular calcium channel called two-pore channel (TPCs) and the hormone oxytocin. Oxytocin is a neurohormone that is well known for its role in social bonding and is released in response to social cues, such as conversation or the sound of a baby crying. Despite the importance of oxytocin, the mechanisms underlying its release remain obscure. Using a mouse model, the study showed that TPCs, which are calcium channels of the endolysosomes (small membrane-bound compartments within cells), play a critical role in controlling oxytocin secretion in the hypothalamus, a region of the brain that regulates hormone release involved in social behavior. The study highlighted that endolysosomal TPCs regulate the amount of oxytocin that is released into the bloodstream and into the brain. More specifically, TPCs seem important in one particular step of the release: the priming of oxytocin vesicles, a process that is poorly understood. Priming is defined by a vesicle moving from the reserve pool (deep in the cell) to the plasma membrane to enable the sustained release of oxytocin. As expected, mice lacking TPCs displayed low plasma levels of oxytocin and social behavior deficits (impaired maternal behavior, social motivation toward novelty and vocalizations). In conclusion, this study provides new insights into the mechanisms underlying the regulation of oxytocin release and social behavior and highlights the potential therapeutic value of targeting endolysosomal TPCs to enhance oxytocin release in the brain since direct hormone replacement often leads to a desensitization of response.

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Why is it important?

The findings of this study have important implications for our understanding of neurohormonal release those controls social behavior and emotions. They suggest that endolysosomal TPCs may be potential targets for the development of new treatments for disorders related to social behavior such as neurodevelopmental disease, anxiety or depression. Therefore, we propose that it would be very valuable to develop molecules to stimulate TPCs to increase the oxytocin levels in individuals with neuropsychiatric conditions such as autism spectrum disorder.


This study was the result of an international collaboration aimed at elucidating the role of TPCs in the brain. Our investigations led us to study the hypothalamus, where we discovered the unexpected role of TPCs in controlling oxytocin release and its impact on regulating social behavior. TPCs have been largely unstudied in the brain until now and there is a wealth of new roles waiting to be discovered. This study breaks new ground by connecting the lesser-known TPCs with the widely recognized hormone oxytocin. In my view, it highlights the beauty of science.

Dr Lora L Martucci
University of Oxford

Read the Original

This page is a summary of: Endolysosomal TPCs regulate social behavior by controlling oxytocin secretion, Proceedings of the National Academy of Sciences, February 2023, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2213682120.
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