C-terminal Src Kinase Gates Homeostatic Synaptic Plasticity and Regulates Fasciclin II Expression at the Drosophila Neuromuscular Junction

PLoS Genetics
Ashlyn M SpringC Andrew Frank

Abstract

Forms of homeostatic plasticity stabilize neuronal outputs and promote physiologically favorable synapse function. A well-studied homeostatic system operates at the Drosophila melanogaster larval neuromuscular junction (NMJ). At the NMJ, impairment of postsynaptic glutamate receptor activity is offset by a compensatory increase in presynaptic neurotransmitter release. We aim to elucidate how this process operates on a molecular level and is preserved throughout development. In this study, we identified a tyrosine kinase-driven signaling system that sustains homeostatic control of NMJ function. We identified C-terminal Src Kinase (Csk) as a potential regulator of synaptic homeostasis through an RNAi- and electrophysiology-based genetic screen. We found that Csk loss-of-function mutations impaired the sustained expression of homeostatic plasticity at the NMJ, without drastically altering synapse growth or baseline neurotransmission. Muscle-specific overexpression of Src Family Kinase (SFK) substrates that are negatively regulated by Csk also impaired NMJ homeostasis. Surprisingly, we found that transgenic Csk-YFP can support homeostatic plasticity at the NMJ when expressed either in the muscle or in the nerve. However, only muscl...Continue Reading

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Citations

Jun 4, 2005·BMC Neuroscience·Paul D EtterMani Ramaswami
Nov 19, 2013·PloS One·William M VanderheydenPaul J Shaw
Sep 27, 2019·Synapse·C Andrew FrankMartin Müller
May 31, 2017·PLoS Genetics·Qiuling LiNicholas Stavropoulos
Aug 4, 2020·Neural Development·Vivian T ChouDavid Van Vactor
Jan 16, 2021·Cellular and Molecular Life Sciences : CMLS·Pragya Goel, Dion Dickman
May 25, 2021·Frontiers in Cellular Neuroscience·Catherine J Yeates, C Andrew Frank

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Datasets Mentioned

BETA
AHN59326.1

Methods Mentioned

BETA
transgenic
fluorescence microscopy
PCR

Software Mentioned

ImageJ
Mini Analysis
Bruchpilot
PhTox
Fiji
Imaris x64
Mini
pCLAMP
Zen software

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