RRC ID 57177
Author Harris N, Fetter RD, Brasier DJ, Tong A, Davis GW.
Title Molecular Interface of Neuronal Innate Immunity, Synaptic Vesicle Stabilization, and Presynaptic Homeostatic Plasticity.
Journal Neuron
Abstract We define a homeostatic function for innate immune signaling within neurons. A genetic analysis of the innate immune signaling genes IMD, IKKβ, Tak1, and Relish demonstrates that each is essential for presynaptic homeostatic plasticity (PHP). Subsequent analyses define how the rapid induction of PHP (occurring in seconds) can be coordinated with the life-long maintenance of PHP, a time course that is conserved from invertebrates to mammals. We define a novel bifurcation of presynaptic innate immune signaling. Tak1 (Map3K) acts locally and is selective for rapid PHP induction. IMD, IKKβ, and Relish are essential for long-term PHP maintenance. We then define how Tak1 controls vesicle release. Tak1 stabilizes the docked vesicle state, which is essential for the homeostatic expansion of the readily releasable vesicle pool. This represents a mechanism for the control of vesicle release, and an interface of innate immune signaling with the vesicle fusion apparatus and homeostatic plasticity.
Volume 100(5)
Pages 1163-1179.e4
Published 2018-12-5
DOI 10.1016/j.neuron.2018.09.048
PII S0896-6273(18)30850-X
PMID 30344041
PMC PMC6283688
MeSH Animals Animals, Genetically Modified Drosophila Proteins / immunology Drosophila melanogaster Female Homeostasis* I-kappa B Kinase / immunology Immunity, Innate* MAP Kinase Kinase Kinases / immunology Male Neuronal Plasticity / immunology* Neurons / immunology* Presynaptic Terminals / immunology* Signal Transduction Synaptic Vesicles / immunology* Transcription Factors / immunology
IF 14.403
Times Cited 10
Resource
Drosophila