Excess glutamate release triggers subunit-specific homeostatic receptor scaling

Autor: Yifu Han, Pragya Goel, Jiawen Chen, Sarah Perry, Nancy Tran, Samantha Nishimura, Manisha Sanjani, Chun Chien, Dion Dickman
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cell Reports, Vol 42, Iss 7, Pp 112775- (2023)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2023.112775
Popis: Summary: Ionotropic glutamate receptors (GluRs) are targets for modulation in Hebbian and homeostatic synaptic plasticity and are remodeled by development, experience, and disease. We have probed the impact of synaptic glutamate levels on the two postsynaptic GluR subtypes at the Drosophila neuromuscular junction, GluRA and GluRB. We first demonstrate that GluRA and GluRB compete to establish postsynaptic receptive fields, and that proper GluR abundance and composition can be orchestrated in the absence of any synaptic glutamate release. However, excess glutamate adaptively tunes postsynaptic GluR abundance, echoing GluR scaling observed in mammalian systems. Furthermore, when GluRA vs. GluRB competition is eliminated, GluRB becomes insensitive to glutamate modulation. In contrast, GluRA is now homeostatically regulated by excess glutamate to maintain stable miniature activity, where Ca2+ permeability through GluRA receptors is required. Thus, excess glutamate, GluR competition, and Ca2+ signaling collaborate to selectively target GluR subtypes for homeostatic regulation at postsynaptic compartments.
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