학술논문
STIM2 regulates NMDA receptor endocytosis that is induced by short-term NMDA receptor overactivation in cortical neurons.
Document Type
Academic Journal
Author
Serwach K; Molecular Biology Unit, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland.; Nurowska E; Department of Pharmacotherapy and Pharmaceutical Care, Centre for Preclinical Research and Technology (CePT), Medical University of Warsaw, Warsaw, Poland.; Klukowska M; Molecular Biology Unit, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland.; Zablocka B; Molecular Biology Unit, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland.; Gruszczynska-Biegala J; Molecular Biology Unit, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland. jgruszczynska@imdik.pan.pl.
Source
Publisher: Springer Country of Publication: Switzerland NLM ID: 9705402 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-9071 (Electronic) Linking ISSN: 1420682X NLM ISO Abbreviation: Cell Mol Life Sci Subsets: MEDLINE
Subject
Language
English
Abstract
Recent findings suggest an important role for the dysregulation of stromal interaction molecule (STIM) proteins, activators of store-operated Ca 2+ channels, and the prolonged activation of N-methyl-D-aspartate receptors (NMDARs) in the development of neurodegenerative diseases. We previously demonstrated that STIM silencing increases Ca 2+ influx through NMDAR and STIM-NMDAR2 complexes are present in neurons. However, the interplay between NMDAR subunits (GluN1, GluN2A, and GluN2B) and STIM1/STIM2 with regard to intracellular trafficking remains unknown. Here, we found that the activation of NMDAR endocytosis led to an increase in STIM2-GluN2A and STIM2-GluN2B interactions in primary cortical neurons. STIM1 appeared to migrate from synaptic to extrasynaptic sites. STIM2 silencing inhibited post-activation NMDAR translocation from the plasma membrane and synaptic spines and increased NMDAR currents. Our findings reveal a novel molecular mechanism by which STIM2 regulates NMDAR synaptic trafficking by promoting NMDAR endocytosis after receptor overactivation, which may suggest protection against excessive uncontrolled Ca 2+ influx through NMDARs.
(© 2023. The Author(s).)
(© 2023. The Author(s).)