WEKO3
アイテム
Proteolytic processing of protein tyrosine phosphatase receptor type Z in the CNS
https://ir.soken.ac.jp/records/1070
https://ir.soken.ac.jp/records/107033234b58-f3ee-4d07-af6d-580f5f99b2aa
| 名前 / ファイル | ライセンス | アクション |
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要旨・審査要旨 / Abstract, Screening Result (186.0 kB)
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本文 / Thesis (10.0 MB)
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| アイテムタイプ | 学位論文 / Thesis or Dissertation(1) | |||||||||||
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| 公開日 | 2010-02-22 | |||||||||||
| タイトル | ||||||||||||
| タイトル | Proteolytic processing of protein tyrosine phosphatase receptor type Z in the CNS | |||||||||||
| 言語 | en | |||||||||||
| 言語 | ||||||||||||
| 言語 | eng | |||||||||||
| 資源タイプ | ||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_46ec | |||||||||||
| 資源タイプ | thesis | |||||||||||
| 著者 |
CHOW, PAKHONG Jeremy
× CHOW, PAKHONG Jeremy
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| 学位授与機関 | ||||||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||||||
| 学位授与機関識別子 | 12702 | |||||||||||
| 学位授与機関名 | 総合研究大学院大学 | |||||||||||
| 言語 | ja | |||||||||||
| 学位名 | ||||||||||||
| 学位名 | 博士（理学） | |||||||||||
| 言語 | ja | |||||||||||
| 学位記番号 | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | 総研大甲第1204号 | |||||||||||
| 言語 | ja | |||||||||||
| 研究科 | ||||||||||||
| 言語 | ja | |||||||||||
| 値 | 生命科学研究科 | |||||||||||
| 専攻 | ||||||||||||
| 言語 | ja | |||||||||||
| 値 | 19 基礎生物学専攻 | |||||||||||
| 学位授与年月日 | ||||||||||||
| 学位授与年月日 | 2008-09-30 | |||||||||||
| 学位授与年度 | ||||||||||||
| 言語 | ja | |||||||||||
| 値 | 2008 | |||||||||||
| 要旨 | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | Protein tyrosine phosphatase receptor type Z (Ptprz, also known as PTPζ or RPTPβ) is<br />preferentially expressed in the brain as a major chondroitin sulfate proteoglycan. <br />Three splicing variants, two receptor-type isoforms and one secretory isoform, are<br />known. Ptprz interacts with the PSD95 family through its intracellular<br />carboxyl-terminal PDZ-binding motif in the postsynaptic density of the adult brain. <br /><i>Ptprz></i>-deficient mice display impairments in spatial and contextual learning. Here, I<br />show that the extracellular region of the receptor isoforms of Ptprz are cleaved by<br />metalloproteinases including ADAM-17 (TACE) and subsequently the<br />membrane-tethered fragment is cleaved by presenilin/γ-secretase, releasing its<br />intracellular region into the cytoplasm: Noteworthily, the intracellular fragment of<br />Ptprz shows nuclear localization. Administration of GM6001, an inhibitor of<br />metalloproteinases, to mice demonstrated the metalloproteinase-mediated cleavage of<br />Ptprz under physiological conditions. Furthermore, I identified the cleavage sites in<br />the extracellular juxtamembrane region of Ptprz by TACE and MMP-9. This is the<br />first evidence of the metalloproteinase-mediated processing of an RPTP in the central<br />nervous system. <br /> I also identified the proteolytic processing of Ptprz by plasmin in the adult mouse<br />brain, which is markedly enhanced after kainate-induced seizures. We estimated the<br />cleavage sites in the extracellular region of Ptprz based on cell-based assays and <i>in vitro</i>digestion experiments with recombinant proteins. The findings indicate that Ptprz is a<br />physiological target for activity-dependent proteolytic processing by the tPA/plasmin<br />system, and suggest that the proteolytic fragments are involved in the structural and<br />functional processes of the synapses during learning and memory. <br /> | |||||||||||
| 所蔵 | ||||||||||||
| 値 | 有 | |||||||||||
| フォーマット | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | application/pdf | |||||||||||
