Drosophila glutamate receptor mRNA expression and mRNP particles

Ganesan, Subhashree; Karr, Julie; Featherstone, David E.

doi:10.4161/rna.8.5.16014

Cited by 11 publications

(5 citation statements)

References 38 publications

(45 reference statements)

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“…3 C). Thus, gluRIIA mRNA does not localise to the NMJ and is found instead in cytoplasmic puncta in agreement with other reports ( Currie et al, 1995; Karr et al, 2009; Ganesan et al, 2011 ). GluRIIA is a transmembrane protein and must be synthesised in the endoplasmic reticulum (ER) before oligomerising with the other subunits during its journey along the secretory pathway through the Golgi apparatus to the plasma membrane ( Barry and Ziff, 2002 ).…”

Section: Resultssupporting

confidence: 93%

Staufen targets coracle mRNA to Drosophila neuromuscular junctions and regulates GluRIIA synaptic accumulation and bouton number

Gardiol

Johnston

2014

Developmental Biology

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The post-synaptic translation of localised mRNAs has been postulated to underlie several forms of plasticity at vertebrate synapses, but the mechanisms that target mRNAs to these postsynaptic sites are not well understood. Here we show that the evolutionary conserved dsRNA binding protein, Staufen, localises to the postsynaptic side of the Drosophila neuromuscular junction (NMJ), where it is required for the localisation of coracle mRNA and protein. Staufen plays a well-characterised role in the localisation of oskar mRNA to the oocyte posterior, where Staufen dsRNA-binding domain 5 is specifically required for its translation. Removal of Staufen dsRNA-binding domain 5, disrupts the postsynaptic accumulation of Coracle protein without affecting the localisation of cora mRNA, suggesting that Staufen similarly regulates Coracle translation. Tropomyosin II, which functions with Staufen in oskar mRNA localisation, is also required for coracle mRNA localisation, suggesting that similar mechanisms target mRNAs to the NMJ and the oocyte posterior. Coracle, the orthologue of vertebrate band 4.1, functions in the anchoring of the glutamate receptor IIA subunit (GluRIIA) at the synapse. Consistent with this, staufen mutant larvae show reduced accumulation of GluRIIA at synapses. The NMJs of staufen mutant larvae have also a reduced number of synaptic boutons. Altogether, this suggests that this novel Staufen-dependent mRNA localisation and local translation pathway may play a role in the developmentally regulated growth of the NMJ.

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Section: Resultssupporting

confidence: 93%

Staufen targets coracle mRNA to Drosophila neuromuscular junctions and regulates GluRIIA synaptic accumulation and bouton number

Gardiol

Johnston

2014

Developmental Biology

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“…In both Drosophila and vertebrate muscles, increases in DNA content are associated with the position of the NMJ. While in vertebrate muscles, this seems to be achieved by regional clustering of nuclei, VL muscles increase nuclear DNA content; however, in both systems, nuclei adjacent to the NMJ express specific genes required for NMJ function (Ganesan et al, 2011;Merlie and Sanes, 1985;Packard et al, 2015;Pavlath et al, 1989;Rosser and Bandman, 2003). Thus, it is likely that, as in mammals, NMJs and MTJs impose distinct functional requirements on adjacent VL nuclei.…”

Section: Discussionmentioning

confidence: 99%

Nuclear Scaling Is Coordinated among Individual Nuclei in Multinucleated Muscle Fibers

et al. 2019

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Graphical Abstract Highlights d Muscle nuclei collectively establish precise global scaling with muscle fiber size d Cells contain domains with distinct local scaling of DNA, nuclear and nucleolar sizes d Nucleolar scaling indicates proportionally higher synthetic activity in small nuclei d Changes in DNA content affect nuclear scaling relationships and muscle function SUMMARY Optimal cell performance depends on cell size and the appropriate relative size, i.e., scaling, of the nucleus. How nuclear scaling is regulated and contributes to cell function is poorly understood, especially in skeletal muscle fibers, which are among the largest cells, containing hundreds of nuclei.Here, we present a Drosophila in vivo system to analyze nuclear scaling in whole multinucleated muscle fibers, genetically manipulate individual components, and assess muscle function. Despite precise global coordination, we find that individual nuclei within a myofiber establish different local scaling relationships by adjusting their size and synthetic activity in correlation with positional or spatial cues. While myonuclei exhibit compensatory potential, even minor changes in global nuclear size scaling correlate with reduced muscle function. Our study provides the first comprehensive approach to unraveling the intrinsic regulation of size in multinucleated muscle fibers. These insights to muscle cell biology will accelerate the development of interventions for muscle diseases.

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“…To date, studies have shown that GluRIIA mRNA aggregates are distributed throughout the muscle (Currie et al 1995;Karr et al 2009;Ganesan et al 2011). The Syp targets we have identified here, such as msp-300, hiw, nrx-1, α-spec, and dlg1, are now excellent candidates for localized expression at the NMJ.…”

Section: Discussionmentioning

confidence: 99%

Drosophila Syncrip modulates the expression of mRNAs encoding key synaptic proteins required for morphology at the neuromuscular junction

McDermott

Halstead

et al. 2014

RNA

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Localized mRNA translation is thought to play a key role in synaptic plasticity, but the identity of the transcripts and the molecular mechanism underlying their function are still poorly understood. Here, we show that Syncrip, a regulator of localized translation in the Drosophila oocyte and a component of mammalian neuronal mRNA granules, is also expressed in the Drosophila larval neuromuscular junction, where it regulates synaptic growth. We use RNA-immunoprecipitation followed by high-throughput sequencing and qRT-PCR to show that Syncrip associates with a number of mRNAs encoding proteins with key synaptic functions, including msp-300, syd-1, neurexin-1, futsch, highwire, discs large, and α-spectrin. The protein levels of MSP-300, Discs large, and a number of others are significantly affected in syncrip null mutants. Furthermore, syncrip mutants show a reduction in MSP-300 protein levels and defects in muscle nuclear distribution characteristic of msp-300 mutants. Our results highlight a number of potential new players in localized translation during synaptic plasticity in the neuromuscular junction. We propose that Syncrip acts as a modulator of synaptic plasticity by regulating the translation of these key mRNAs encoding synaptic scaffolding proteins and other important components involved in synaptic growth and function.

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Drosophila glutamate receptor mRNA expression and mRNP particles

Cited by 11 publications

References 38 publications

Staufen targets coracle mRNA to Drosophila neuromuscular junctions and regulates GluRIIA synaptic accumulation and bouton number

Staufen targets coracle mRNA to Drosophila neuromuscular junctions and regulates GluRIIA synaptic accumulation and bouton number

Nuclear Scaling Is Coordinated among Individual Nuclei in Multinucleated Muscle Fibers

Drosophila Syncrip modulates the expression of mRNAs encoding key synaptic proteins required for morphology at the neuromuscular junction

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