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Overexpression of Dyrk1A Causes the Defects in Synaptic Vesicle Endocytosis

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Authors
Kim, Yoonju; Park, Joohyun; Chang, Sunghoe; Song, Woo-Joo
Issue Date
2010
Publisher
KARGER
Citation
NEUROSIGNALS; Vol.18 3; 164-172
Keywords
Dyrk1ADown syndromeSynaptic vesicleEndocytic proteinsPhosphorylationClathrin-mediated endocytosis
Abstract
Trisomy 21-linked Dyrk1A (dual-specificity tyrosine phosphorylation-regulated kinase 1A) overexpression is implicated in pathogenic mechanisms underlying mental retardation in Down syndrome (DS). It is known to phosphorylate multiple substrates including endocytic proteins in vitro, but the functional consequence of Dyrk1A-mediated phosphorylation on endocytosis has never been investigated. Here, we show that overexpression of Dyrk1A causes defects in clathrin-mediated endocytosis and specifically, in the recruitment of endocytic proteins to clathrin-coated pits in fibroblasts. Synaptic vesicle endocytosis also significantly slowed down as a result of Dyrk1A overexpression in cultured hippocampal neurons. These effects are dependent on Dyrk1A kinase activity. The inhibitory effect of Dyrk1A on synaptic vesicle endocytosis was confirmed in neuronal cultures derived from transgenic mice overexpressing Dyrk1A at levels found in DS. Pharmacological blockade of Dyrk1A with epigallocatechin gallate rescued the endocytic phenotypes found in transgenic neurons. Together, our results suggest that aberrant Dyrk1A-mediated phosphorylation of the endocytic machinery perturbs synaptic vesicle endocytosis, which may contribute to synaptic dysfunctions and cognitive deficits associated with DS. Copyright (C) 2010 S. Karger AG, Basel
ISSN
1424-862X
Language
English
URI
http://hdl.handle.net/10371/76391
DOI
https://doi.org/10.1159/000321994
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Physiology (생리학교실)Journal Papers (저널논문_생리학교실)
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