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Overexpression of Dyrk1A Causes the Defects in Synaptic Vesicle Endocytosis

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dc.contributor.authorKim, Yoonju-
dc.contributor.authorPark, Joohyun-
dc.contributor.authorChang, Sunghoe-
dc.contributor.authorSong, Woo-Joo-
dc.date.accessioned2012-05-24T02:42:24Z-
dc.date.available2012-05-24T02:42:24Z-
dc.date.issued2010-
dc.identifier.citationNEUROSIGNALS; Vol.18 3; 164-172ko_KR
dc.identifier.issn1424-862X-
dc.identifier.urihttps://hdl.handle.net/10371/76391-
dc.description.abstractTrisomy 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, Baselko_KR
dc.description.sponsorshipThis research was supported by a grant of the Korea Healthcare
technology R&D Project (A084393) to S.C. from the Ministry
for Health, Welfare & Family Affairs, Republic of Korea. Confocal
and TIRF microscopy data for this study were acquired and analyzed
in the Biomedical Imaging Center at Seoul National University
College of Medicine.
ko_KR
dc.language.isoenko_KR
dc.publisherKARGERko_KR
dc.subjectDyrk1Ako_KR
dc.subjectDown syndromeko_KR
dc.subjectSynaptic vesicleko_KR
dc.subjectEndocytic proteinsko_KR
dc.subjectPhosphorylationko_KR
dc.subjectClathrin-mediated endocytosisko_KR
dc.titleOverexpression of Dyrk1A Causes the Defects in Synaptic Vesicle Endocytosisko_KR
dc.typeArticleko_KR
dc.contributor.AlternativeAuthor김윤주-
dc.contributor.AlternativeAuthor송우주-
dc.contributor.AlternativeAuthor장성호-
dc.contributor.AlternativeAuthor박주현-
dc.identifier.doi10.1159/000321994-
dc.citation.journaltitleNEUROSIGNALS-
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