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Nahm, M., Lee, M.J., Parkinson, W., Lee, M., Kim, H., Kim, Y.J., Kim, S., Cho, Y.S., Min, B.M., Bae, Y.C., Broadie, K., Lee, S. (2013). Spartin Regulates Synaptic Growth and Neuronal Survival by Inhibiting BMP-Mediated Microtubule Stabilization.  Neuron 77(4): 680--695.
FlyBase ID
FBrf0220896
Publication Type
Research paper
Abstract

Troyer syndrome is a hereditary spastic paraplegia caused by human spartin (SPG20) gene mutations. We have generated a Drosophila disease model showing that Spartin functions presynaptically with endocytic adaptor Eps15 to regulate synaptic growth and function. Spartin inhibits bone morphogenetic protein (BMP) signaling by promoting endocytic degradation of BMP receptor wishful thinking (Wit). Drosophila fragile X mental retardation protein (dFMRP) and Futsch/MAP1B are downstream effectors of Spartin and BMP signaling in regulating microtubule stability and synaptic growth. Loss of Spartin or elevation of BMP signaling induces age-dependent progressive defects resembling hereditary spastic paraplegias, including motor dysfunction and brain neurodegeneration. Null spartin phenotypes are prevented by administration of the microtubule-destabilizing drug vinblastine. Together, these results demonstrate that Spartin regulates both synaptic development and neuronal survival by controlling microtubule stability via the BMP-dFMRP-Futsch pathway, suggesting that impaired regulation of microtubule stability is a core pathogenic component in Troyer syndrome.

PubMed ID
PubMed Central ID
PMC3815429 (PMC) (EuropePMC)
Related Publication(s)
Note

Is instability good for the brain?
Carrillo et al., 2013, Neuron 77(4): 599--601 [FBrf0220933]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Neuron
    Title
    Neuron
    Publication Year
    1988-
    ISBN/ISSN
    0896-6273
    Data From Reference
    Aberrations (1)
    Alleles (20)
    Gene Groups (1)
    Genes (22)
    Human Disease Models (1)
    Physical Interactions (3)
    Cell Lines (1)
    Natural transposons (1)
    Insertions (3)
    Experimental Tools (3)
    Transgenic Constructs (10)