Science (New York, N.Y.) · 2025
The synaptic ectokinase VLK triggers the EphB2-NMDAR interaction to drive injury-induced pain.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Srikanth Kolluru D, Elahi Hajira, Chander Praveen, Washburn Halley R, Hassler Shayne, Mwirigi Juliet M, Kume Moeno, Loucks Jessica, Arjarapu Rohita, Hodge Rachel, He Lucy, Mazhar Khadijah, Shiers Stephanie I, Sankaranarayanan Ishwarya, Erdjument-Bromage Hediye, Neubert Thomas A, Dougherty Patrick M, Campbell Zachary T, Paik Raehum, Price Theodore J, Dalva Matthew B
Аннотация
Phosphorylation of hundreds of protein extracellular domains is mediated by two kinase families but the functional role of these kinases is underexplored. We find that the presynaptic release of the tyrosine-directed ectokinase, vertebrate lonesome kinase (VLK/Pkdcc), is necessary and sufficient for the direct extracellular interaction between EphB2 and GluN1 at synapses for phosphorylation of the ectodomain of EphB2 and mediation of injury-induced pain. Pkdcc is an essential gene in the nervous system, and VLK is enriched at synapses and released from neurons in an activity- and soluble N-ethylmaleimide-sensitive factor activating protein receptor (SNARE)-dependent manner to drive extracellular interactions. Our results show that presynaptic sensory neuron-specific VLK knockout attenuates postsurgical pain in mice without changing sensorimotor performance, suggesting that VLK critically regulates synaptic protein-protein interactions and acute pain in response to injury.