PAT1 induces cell death signal and SET mislocalization into the cytoplasm by increasing APP/APLP2 at the cell surface
| Autor: | Bernadette Allinquant, Stéphanie Briand, Sanjay W. Pimplikar, Alexandra Madeira, Patricia Facchinetti, Jean Michel Pommet, Christine Clamagirand |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Cytoplasm
Aging Programmed cell death Amino Acid Transport Systems media_common.quotation_subject Cell Down-Regulation Apoptosis Nerve Tissue Proteins Oligodeoxyribonucleotides Antisense Amyloid beta-Protein Precursor Mice In Situ Nick-End Labeling Amyloid precursor protein medicine Animals Humans Biotinylation Histone Chaperones RNA Small Interfering Internalization Cells Cultured Caspase media_common Cerebral Cortex Neurons Symporters biology General Neuroscience Cell Membrane Embryo Mammalian Subcellular localization Protein Structure Tertiary Cell biology DNA-Binding Proteins Protein Transport medicine.anatomical_structure Caspases biology.protein Neurology (clinical) Geriatrics and Gerontology Neuroscience Transcription Factors Developmental Biology |
| Zdroj: | Neurobiology of Aging. 32:1099-1113 |
| ISSN: | 0197-4580 |
| DOI: | 10.1016/j.neurobiolaging.2009.05.021 |
| Popis: | The cleavage of amyloid precursor protein (APP) by caspases unmasks a domain extending from membrane to caspase cleavage site. This domain induces apoptosis in vitro and in vivo when overexpressed in neurons through the help of an internalization vector. In this model, we previously showed that SET rapidly binds to the internalized domain and is involved in downstream deleterious effects. Under these conditions SET mislocalizes from the nucleus to the cytoplasm, as in Alzheimer's disease (AD). In this report using the same model, we show that PAT1 attaches to the internalized domain earlier than SET and that this binding causes an increase in the levels of APP and APLP2 at the cell surface. Down regulation experiments of PAT1 and of APP and APLP2 show that the increase of the levels of APP and APLP2 at the cell surface triggers the cell death signal and SET mislocalization into the cytoplasm. In the context of AD these data suggest that mislocalization of SET into the cytoplasm may occur downstream of first cell death signal events involving PAT1 protein. |
| Databáze: | OpenAIRE |
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