title: Activity-dependent phosphorylation of dynamin 1 at serine 857.
abstract: Dynamin 1 is thought to mediate synaptic transmission through interactions with multiple endocytic accessory proteins in a phosphorylation-dependent manner. Previously, we have shown that DYRK1A, a chromosome 21-encoded kinase implicated in the mental retardation of Down syndrome, phosphorylates primarily serine 857 (S857) in the proline-rich domain, found only in 1xa, one of the alternative C-terminal splicing isoforms of dynamin 1. Dynamin 1xa and 1xb isoforms are able to assemble into heterologous complexes and are coregulated by DYRK1A phosphorylation in binding to amphiphysin in vitro. To help in assessing the physiological significance of S857 phosphorylation, we developed a semiquantitative method for measuring the cellular level of phospho-S857 (pS857). Dynamin 1xa is highly phosphorylated at S857 in resting hippocampal neurons and in a hippocampal cell line, with >60% of all endogenous protein phosphorylated at this residue. In the hippocampus, the level of pS857 is dynamically controlled by synaptic stimulations with the involvement of Ca(2+)/calcineurin and AMPA/kainate receptors. Immunofluorescence staining shows that pS857 is found in the soma and throughout the entire length of apical dendrites in resting pyramidal neurons. Neuronal stimulation in the Schaffer collateral pathway promotes pS857 dephosphorylation in distal areas of apical dendrites, the region forming synapses with the impinging axons of Schaffer collateral. In summary, our results support the conclusion that S857 phosphorylation is a physiological event and its level is modulated by neuronal activity in nerve terminals.
authors.affiliation: Department of Biology, College of Staten Island, City University of New York, Staten Island, NY 10314, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Xie
authors.forename: Tatyana
authors.initials: T
authors.lastname: Adayev
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Zhu
authors.forename: Jerzy
authors.initials: J
authors.lastname: Wegiel
authors.forename: Andrzej
authors.initials: A
authors.lastname: Wieraszko
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Hwang
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D034284:Dynamin I / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D012694:Serine / Q000235:genetics / Q000378:metabolism*
chemical_list: D012694:Serine; D034284:Dynamin I