Akt regulates glutamate receptor trafficking and postsynaptic membrane elaboration at the <i>Drosophila</i> neuromuscular junction

Lee, Hyun Gwan; Zhao, Na; Nguyen, Michelle M.; Selleck, Scott B.

doi:10.1002/dneu.22086

Cited by 11 publications

(8 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For neuroblast overexpression Pros-GAL4 was obtained from the putative-enhancer collection (Bloomington Drosophila Stock Centre [BDSC] at Indiana University, USA). Flies expressing UAS driven shRNA targeting AKT1 (P(KK100495)VIE-260B ; Vienna Drosophila RNAi Center, Vienna) were crossed to flies with a GAL4 driver expressed in neuroblasts ( Insu-GAL4 , gift from Jürgen Knoblich) ( AKT1 RNAi line previously characterised by Lee et al, 2013 ).…”

Section: Methodsmentioning

confidence: 99%

Nucleotide synthesis is regulated by cytoophidium formation during neurodevelopment and adaptive metabolism

et al. 2014

View full text Add to dashboard Cite

The essential metabolic enzyme CTP synthase (CTPsyn) can be compartmentalised to form an evolutionarily-conserved intracellular structure termed the cytoophidium. Recently, it has been demonstrated that the enzymatic activity of CTPsyn is attenuated by incorporation into cytoophidia in bacteria and yeast cells. Here we demonstrate that CTPsyn is regulated in a similar manner in Drosophila tissues in vivo. We show that cytoophidium formation occurs during nutrient deprivation in cultured cells, as well as in quiescent and starved neuroblasts of the Drosophila larval central nervous system. We also show that cytoophidia formation is reversible during neurogenesis, indicating that filament formation regulates pyrimidine synthesis in a normal developmental context. Furthermore, our global metabolic profiling demonstrates that CTPsyn overexpression does not significantly alter CTPsyn-related enzymatic activity, suggesting that cytoophidium formation facilitates metabolic stabilisation. In addition, we show that overexpression of CTPsyn only results in moderate increase of CTP pool in human stable cell lines. Together, our study provides experimental evidence, and a mathematical model, for the hypothesis that inactive CTPsyn is incorporated into cytoophidia.

show abstract

Section: Methodsmentioning

confidence: 99%

Nucleotide synthesis is regulated by cytoophidium formation during neurodevelopment and adaptive metabolism

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Dorsal acts along with inhibitory molecule IĸB/Cactus and kinase IRAK/ Pelle to regulate A-type receptor density (Cantera et al 1999;Heckscher et al 2007). The serine/threonine kinase Akt also promotes A-type receptor levels, and may do so by regulating the levels of Dorsal and Cactus at the synapse (Lee et al 2013a). It is unclear how Dorsal, Cactus, and Pelle affect GluRs.…”

Section: Ionotropic Glutamate Receptors At the Nmjmentioning

confidence: 99%

Transmission, Development, and Plasticity of Synapses

Harris¹,

2015

View full text Add to dashboard Cite

Chemical synapses are sites of contact and information transfer between a neuron and its partner cell. Each synapse is a specialized junction, where the presynaptic cell assembles machinery for the release of neurotransmitter, and the postsynaptic cell assembles components to receive and integrate this signal. Synapses also exhibit plasticity, during which synaptic function and/or structure are modified in response to activity. With a robust panel of genetic, imaging, and electrophysiology approaches, and strong evolutionary conservation of molecular components, Drosophila has emerged as an essential model system for investigating the mechanisms underlying synaptic assembly, function, and plasticity. We will discuss techniques for studying synapses in Drosophila, with a focus on the larval neuromuscular junction (NMJ), a well-established model glutamatergic synapse. Vesicle fusion, which underlies synaptic release of neurotransmitters, has been well characterized at this synapse. In addition, studies of synaptic assembly and organization of active zones and postsynaptic densities have revealed pathways that coordinate those events across the synaptic cleft. We will also review modes of synaptic growth and plasticity at the fly NMJ, and discuss how pre-and postsynaptic cells communicate to regulate plasticity in response to activity. KEYWORDS FlyBook; Drosophila; synapse; neurotransmitter release; synaptic plasticity; active zone; synaptic vesicle TABLE OF CONTENTS Abstract 345Introduction 345

show abstract

“…This is also true for PKC, which may be mediated through PI3K. A canonical pathway of PI3K is through activation of PKB/Akt, which can regulate plasma membrane protein trafficking (Lee et al, 2013). Drugs such as riluzole and volatile anesthetics (such as isoflurane, depicted above) can increase EAAT3 surface expression through a PKC-sensitive mechanism.…”

Section: Figurementioning

confidence: 99%

The importance of the excitatory amino acid transporter 3 (EAAT3)

Bjørn‐Yoshimoto

Underhill

2016

Neurochemistry International

View full text Add to dashboard Cite

The neuronal excitatory amino acid transporter 3 (EAAT3) is fairly ubiquitously expressed in the brain, though it does not necessarily maintain the same function everywhere. It is important in maintaining low local concentrations of glutamate, where its predominant post-synaptic localization can buffer nearby glutamate receptors and modulate excitatory neurotransmission and synaptic plasticity. It is also the main neuronal cysteine uptake system acting as the rate-limiting factor for the synthesis of glutathione, a potent antioxidant, in EAAT3 expressing neurons, while on GABAergic neurons, it is important in supplying glutamate as a precursor for GABA synthesis. Several diseases implicate EAAT3, and modulation of this transporter could prove a useful therapeutic approach. Regulation of EAAT3 could be targeted at several points for functional modulation, including the level of transcription, trafficking and direct pharmacological modulation, and indeed, compounds and experimental treatments have been identified that regulate EAAT3 function at different stages, which together with observations of EAAT3 regulation in patients is giving us insight into the endogenous function of this transporter, as well as the consequences of altered function. This review summarizes work done on elucidating the role and regulation of EAAT3.

show abstract

Akt regulates glutamate receptor trafficking and postsynaptic membrane elaboration at the Drosophila neuromuscular junction

Cited by 11 publications

References 68 publications

Nucleotide synthesis is regulated by cytoophidium formation during neurodevelopment and adaptive metabolism

Nucleotide synthesis is regulated by cytoophidium formation during neurodevelopment and adaptive metabolism

Transmission, Development, and Plasticity of Synapses

The importance of the excitatory amino acid transporter 3 (EAAT3)

Contact Info

Product

Resources

About