دورية أكاديمية
The degradation (by distinct pathways) of human D-amino acid oxidase and its interacting partner pLG72--two key proteins in D-serine catabolism in the brain.
| العنوان: | The degradation (by distinct pathways) of human D-amino acid oxidase and its interacting partner pLG72--two key proteins in D-serine catabolism in the brain. |
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| المؤلفون: | CAPPELLETTI, PAMELA, CAMPOMENOSI, PAOLA, POLLEGIONI, LOREDANO, SACCHI, SILVIA |
| المساهمون: | Cappelletti, Pamela, Campomenosi, Paola, Pollegioni, Loredano, Sacchi, Silvia |
| سنة النشر: | 2014 |
| المجموعة: | IRInSubria - Institutional Repository Insubria (Università degli Studi dell’Insubria) |
| مصطلحات موضوعية: | Bacterial Protein, genetics/metabolism, Brain, drug effects/enzymology/metabolism, Carrier Protein, Cell Line, Tumor, Cytosol, enzymology/metabolism, D-Amino-Acid Oxidase, Endosome, Green Fluorescent Protein, Humans, Luminescent Protein, Lysosome, Mitochondria, Nerve Tissue Protein, Neuron, Peroxisome, Protease Inhibitor, pharmacology, Proteasome Endopeptidase Complex, drug effects, Protein Stability, Proteolysi, Recombinant Fusion Proteins, Ubiquitination |
| الوصف: | Human D-amino acid oxidase (EC 1.4.3.3; hDAAO) is a peroxisomal flavoenzyme significantly enriched in the mammalian brain. hDAAO has been proposed to play (with serine racemase; EC 5.1.1.18) an essential role in the catabolism of D-serine, an 'atypical' key signalling molecule that acts as allosteric activator of the N-methyl-D-aspartate-type glutamate receptor (NMDAr). hDAAO and its interacting partner pLG72 have been related to schizophrenia, a highly disabling psychiatric disorder in which a dysfunction of NMDA-mediated neurotransmission is widely assumed to occur. We previously demonstrated that the D-serine cellular concentration depends on hDAAO and pLG72 expression levels and that newly-synthesized hDAAO interacts with its modulator in the cytosol, being progressively destabilized and inactivated. To obtain insight into the mechanisms regulating cellular D-serine levels, we investigated the degradation pathways of hDAAO and pLG72 in U87 glioblastoma cells stably expressing enhanced yellow fluorescent protein-hDAAO (peroxisomal), hDAAO-enhanced yellow fluorescent protein (cytosolic) or pLG72-enhanced cyan fluorescent protein (mitochondrial) proteins. hDAAO is a long-lived protein: the peroxisomal fraction of this flavoprotein is degraded via the lysosomal/endosomal pathway (and blocking this pathway increases the cellular hDAAO activity and decreases D-serine levels), whereas the cytosolic portion is ubiquitinated and targeted to the proteasome. By contrast, pLG72 shows a rapid turnover (t(1/2) ≈ 25-40 min) and is degraded via the proteasome system, albeit not ubiquitinated. Overexpression of pLG72 increases the turnover of hDAAO, in turn playing a protective role against excessive D-serine depletion. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/24237903; info:eu-repo/semantics/altIdentifier/wos/WOS:000336732600006; volume:281; firstpage:708; lastpage:723; journal:THE FEBS JOURNAL; http://hdl.handle.net/11383/1883143Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84897042700; http://dx.doi.org/10.1111/febs.12616Test |
| DOI: | 10.1111/febs.12616 |
| الإتاحة: | https://doi.org/10.1111/febs.12616Test http://hdl.handle.net/11383/1883143Test |
| رقم الانضمام: | edsbas.E72049E |
| قاعدة البيانات: | BASE |
| DOI: | 10.1111/febs.12616 |
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