title: Abnormal phosphorylation of synapsin I predicts a neuronal transmission impairment in the R6/2 Huntington's disease transgenic mice.
abstract: 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 neurotransmission in HD.
authors.affiliation: Medical and Molecular Genetics, GKT School of Medicine, London SE1 9RT, United Kingdom.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Liévens
authors.forename: Benjamin
authors.initials: B
authors.lastname: Woodman
authors.forename: Amarbirpal
authors.initials: A
authors.lastname: Mahal
authors.forename: Gillian P
authors.initials: GP
authors.lastname: Bates
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D010766:Phosphorylation; D016704:Synapsins / Q000378:metabolism*; D009435:Synaptic Transmission
chemical_list: D016900:Neurofilament Proteins; D016704:Synapsins; C051774:neurofilament protein H; D020928:Mitogen-Activated Protein Kinases; D019703:Calcineurin