A Dual Role for the Adaptor Protein DRK in<i>Drosophila</i>Olfactory Learning and Memory

Moressis, Anastasios; Friedrich, Anette; Pavlopoulos, Elias; Davis, Ronald L.; Skoulakis, Efthimios M. C.

doi:10.1523/jneurosci.3670-08.2009

Cited by 38 publications

(39 citation statements)

References 101 publications

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“…These data suggest that microRNA patways acting on filamin A mRNA and/or other processes might be responsible for these behavioral phenotypes. Finally, a recent study by Kanellopoulos et al showed that dFmr1 mutant heterozygotes exhibited a robust learning deficit under sensitive conditions of limited US/CS stimulus pairings (Moressis et al 2009) and verified that under the typically used extended training conditions (Bolduc et al 2008) these flies appear normal. In this study, using genetic and pharmacological tools, it was found that the effects of increased mGluR levels upon dFMRP reduction are linked to reduced cAMP, which in turn likely results in the associative learning and memory deficits (Kanellopoulos et al 2012).…”

Section: Behavioral Phenotypes Of Fxs Wwwlearnmemorgmentioning

confidence: 78%

Learning and behavioral deficits associated with the absence of the fragile X mental retardation protein: what a fly and mouse model can teach us

2014

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The Fragile X syndrome (FXS) is the most frequent form of inherited mental disability and is considered a monogenic cause of autism spectrum disorder. FXS is caused by a triplet expansion that inhibits the expression of the FMR1 gene. The gene product, the Fragile X Mental Retardation Protein (FMRP), regulates mRNA metabolism in brain and nonneuronal cells. During brain development, FMRP controls the expression of key molecules involved in receptor signaling, cytoskeleton remodeling, protein synthesis and, ultimately, spine morphology. Symptoms associated with FXS include neurodevelopmental delay, cognitive impairment, anxiety, hyperactivity, and autistic-like behavior. Twenty years ago the first Fmr1 KO mouse to study FXS was generated, and several years later other key models including the mutant Drosophila melanogaster, dFmr1, have further helped the understanding of the cellular and molecular causes behind this complex syndrome. Here, we review to which extent these biological models are affected by the absence of FMRP, pointing out the similarities with the observed human dysfunction. Additionally, we discuss several potential treatments under study in animal models that are able to partially revert some of the FXS abnormalities.

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Section: Behavioral Phenotypes Of Fxs Wwwlearnmemorgmentioning

confidence: 78%

Learning and behavioral deficits associated with the absence of the fragile X mental retardation protein: what a fly and mouse model can teach us

2014

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“…Training and testing were performed in complete darkness, with dim red light used only during manipulations not requiring exposure to odors. The standard T-maze was modified by replacing the odorant holding cups (20) with glass cylinders of 2.25 cm diameter and 14 cm height as described previously (19,40). An air stream of 600 mL/min passing over the meniscus carried the odors to the maze arms via silicon rubber tubing.…”

Section: Methodsmentioning

confidence: 99%

Molecular vibration-sensing component in Drosophila melanogaster olfaction

Franco

Turin

Mershin

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

176

218

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A common explanation of molecular recognition by the olfactory system posits that receptors recognize the structure or shape of the odorant molecule. We performed a rigorous test of shape recognition by replacing hydrogen with deuterium in odorants and asking whether Drosophila melanogaster can distinguish these identically shaped isotopes. We report that flies not only differentiate between isotopic odorants, but can be conditioned to selectively avoid the common or the deuterated isotope. Furthermore, flies trained to discriminate against the normal or deuterated isotopes of a compound, selectively avoid the corresponding isotope of a different odorant. Finally, flies trained to avoid a deuterated compound exhibit selective aversion to an unrelated molecule with a vibrational mode in the energy range of the carbon-deuterium stretch. These findings are inconsistent with a shape-only model for smell, and instead support the existence of a molecular vibrationsensing component to olfactory reception.

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“…marker could be reduced during Tau accumulation. Thus, we used an additional unrelated antigenic marker, the adaptor protein Drk, which is also preferentially expressed in ␣, ␤, and ␥ lobes of the MBs (Crittenden et al, 1998;Moressis et al, 2009). Again, remnants of few ␣ and ␤ neurons (compare Fig.…”

Section: Ablation Of the Mushroom Bodies Upon Pan-neuronal Accumulatimentioning

confidence: 99%

Differential Effects of Tau on the Integrity and Function of Neurons Essential for Learning in Drosophila

Kosmidis¹,

Grammenoudi²,

Papanikolopoulou³

et al. 2010

J. Neurosci.

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Tauopathies are a heterogeneous group of neurodegenerative dementias involving perturbations in the levels, phosphorylation, or mutations of the microtubule-binding protein Tau. The heterogeneous pathology in humans and model organisms suggests differential susceptibility of neuronal types to wild-type (WT) and mutant Tau. WT and mutant human Tau-encoding transgenes expressed panneuronally in the Drosophila CNS yielded specific and differential toxicity in the embryonic neuroblasts that generate the mushroom body (MB) neurons, suggesting cell type-specific effects of Tau in the CNS. Frontotemporal dementia with parkinsonism-17-linked mutant isoforms were significantly less toxic in MB development. Tau hyperphosphorylation was essential for these MB aberrations, and we identified two novel putative phosphorylation sites, Ser 238 and Thr 245, on WT hTau essential for its toxic effects on MB integrity. Significantly, blocking putative Ser 238 and Thr 245 phosphorylation yielded animals with apparently structurally normal but profoundly dysfunctional MBs, because animals accumulating this mutant protein exhibited strongly impaired associative learning.Interestingly, the mutant protein was hyperphosphorylated at epitopes typically associated with toxicity and neurodegeneration, such as AT8, AT100, and the Par-1 targets Ser 262 and Ser 356 , suggesting that these sites in the context of adult intact MBs mediate dysfunction and occupation of these sites may precede the toxicity-associated Ser 238 and Thr 245 phosphorylation. The data support the notion that phosphorylation at particular sites rather than hyperphosphorylation per se mediates toxicity or dysfunction in a cell type-specific manner.

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A Dual Role for the Adaptor Protein DRK inDrosophilaOlfactory Learning and Memory

Cited by 38 publications

References 101 publications

Learning and behavioral deficits associated with the absence of the fragile X mental retardation protein: what a fly and mouse model can teach us

Learning and behavioral deficits associated with the absence of the fragile X mental retardation protein: what a fly and mouse model can teach us

Molecular vibration-sensing component in Drosophila melanogaster olfaction

Differential Effects of Tau on the Integrity and Function of Neurons Essential for Learning in Drosophila

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