Abnormal phosphorylation of synapsin I predicts a neuronal transmission impairment in the R6/2 Huntington's disease transgenic mice
Abnormal phosphorylation of synapsin I predicts a neuronal transmission impairment in the R6/2 Huntington's disease transgenic mice
复制标题
DOI：
10.1006/mcne.2002.1152
复制
发表时间：
2002-08-01
影响因子：
3.5
通讯作者：
Bates, GP
中科院分区：
文献类型：
--
作者：
Liévens, JC;Woodman, B;Bates, GP
Motor and cognitive deficits in Huntington's disease (HD) are likely caused by progressive neuronal dysfunction preceding neuronal cell death. Synapsin I is one of the major phosphoproteins regulating neurotransmitter release. We report here an abnormal phosphorylation state of synapsin I in the striatum and the cerebral cortex of R6/2 transgenic mice expressing the HD mutation. These changes are mostly characterized by an early overphosphorylation at sites 3-5, whereas phosphorylation at site 1 remains unchanged and at site 6 becomes reduced only close to the end stage of the disease. Such changes do not result from modification in protein expression levels. However, we show a decreased expression of the calcineurin regulatory subunit-B, which may contribute to an imbalance between kinase and phosphatase activities. Together the results suggest that an early impairment in synapsin phosphorylation-dephosphorylation may alter synaptic vesicle trafficking and lead to defective neuro-transmission in HD.
