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Citation
Steinert, J.R., Campesan, S., Richards, P., Kyriacou, C.P., Forsythe, I.D., Giorgini, F. (2012). Rab11 rescues synaptic dysfunction and behavioural deficits in a Drosophila model of Huntington's disease.  Hum. Mol. Genet. 21(13): 2912--2922.
FlyBase ID
FBrf0218528
Publication Type
Research paper
Abstract

Synapse abnormalities in Huntington's disease (HD) patients can precede clinical diagnosis and neuron loss by decades. The polyglutamine expansion in the huntingtin (htt) protein that underlies this disorder leads to perturbations in many cellular pathways, including the disruption of Rab11-dependent endosomal recycling. Impairment of the small GTPase Rab11 leads to the defective formation of vesicles in HD models and may thus contribute to the early stages of the synaptic dysfunction in this disorder. Here, we employ transgenic Drosophila melanogaster models of HD to investigate anomalies at the synapse and the role of Rab11 in this pathology. We find that the expression of mutant htt in the larval neuromuscular junction decreases the presynaptic vesicle size, reduces quantal amplitudes and evoked synaptic transmission and alters larval crawling behaviour. Furthermore, these indicators of early synaptic dysfunction are reversed by the overexpression of Rab11. This work highlights a potential novel HD therapeutic strategy for early intervention, prior to neuronal loss and clinical manifestation of disease.

PubMed ID
PubMed Central ID
PMC3373239 (PMC) (EuropePMC)
Related Publication(s)
Note

Rab11 as a modulator of synaptic transmission.
Giorgini and Steinert, 2013, Commun. Integr. Biol. 6(6): e26807 [FBrf0224156]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Hum. Mol. Genet.
    Title
    Human Molecular Genetics
    Publication Year
    1992-
    ISBN/ISSN
    0964-6906
    Data From Reference
    Alleles (7)
    Genes (3)
    Human Disease Models (1)
    Insertions (2)
    Transgenic Constructs (5)