biostudies-literatureNahm MNIMH NIH HHS680-95https://www.ebi.ac.uk/biostudies/studies/S-EPMC3815429biostudies-literatureUnknown77(4)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 preNeuronSpartin regulates synaptic growth and neuronal survival by inhibiting BMP-mediated microtubule stabilization.PMC3815429R01 MH096832R01MH096832Kim SCho YSBae YCLee SNahm MParkinson WKim HMin BMLee MKim YJLee MJBroadie KfalseSpartin regulates synaptic growth and neuronal survival by inhibiting BMP-mediated microtubule stabilization.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 pre2013-01-01T00:00:00Z2013 Feb2025-04-18T14:07:34.943Z2019-03-27T01:17:58ZS-EPMC38154292343912110.1016/j.neuron.2012.12.015