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P4‐288: α‐synuclein regulates neurite outgrowth through the transcriptional regulation of CDC42
Author(s) -
Kim Seonghan,
Kim Ka Young,
Lee Sang Hyung,
Suh Yoo-Hun
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.2357
Subject(s) - neurite , microbiology and biotechnology , alpha synuclein , biology , cdc42 , immunoprecipitation , chromatin immunoprecipitation , cytoplasm , promoter , genetics , gtpase , gene expression , gene , parkinson's disease , pathology , medicine , in vitro , disease
disease. Particularly, neuron cells in brains of neurodegenerative disease contained autophagic vacuoles as well as precipitates (aggregates) of various proteins characteristically. We want to know what kind of mechanism for survival break out in autophagic condition or for blocking of neuron cell death, what mechanism is triggered. Methods: In autophagic condition, we definitely detected that alpha-synuclein from cytoplasm is translocated to nucleus in neuron cells. In this study, we describe for the first time physical, direct interaction of alpha-synuclein with nuclear cargo protein KPNA that is the nuclear translocation mechanism of alpha-synuclein. We explored the functional consequences of this interaction on neuron cell survival by cell based transfection and gene knock-down experiments(Sh RNA). It was confirmed using GST-pull down assay, Immunoprecipitation, FRET methods. Results: With confocal microscopy, we definitely detected a-synuclein can translocate to nucleus in autophagy. In the results of GST-pull down assay and Immunoprecipitation, a-synuclein can interact with KPNA6 and this interaction cannot detected to between recombinant proteins. We also observed this interaction by FRET (Fluorescence resonance energy transfer). Conclusions: For passing the wicket NPC (Nuclear Pore Complex) a-synuclein bind with KPNA 6. This interaction needs some modification because just recombinant a-synuclein cannot interact with KPNA 6. Nuclear translocation resulted to anti-proliferative effect and furthermore it was related to survival mechanism.