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Ptprz interacts with the PSD95 family through its intracellular\u003cbr /\u003ecarboxyl-terminal PDZ-binding motif in the postsynaptic density of the adult brain. \u003cbr /\u003e\u003ci\u003ePtprz\u003e\u003c/i\u003e-deficient mice display impairments in spatial and contextual learning. Here, I\u003cbr /\u003eshow that the extracellular region of the receptor isoforms of Ptprz are cleaved by\u003cbr /\u003emetalloproteinases including ADAM-17 (TACE) and subsequently the\u003cbr /\u003emembrane-tethered fragment is cleaved by presenilin/\u0026gamma;-secretase, releasing its\u003cbr /\u003eintracellular region into the cytoplasm: Noteworthily, the intracellular fragment of\u003cbr /\u003ePtprz shows nuclear localization. Administration of GM6001, an inhibitor of\u003cbr /\u003emetalloproteinases, to mice demonstrated the metalloproteinase-mediated cleavage of\u003cbr /\u003ePtprz under physiological conditions. Furthermore, I identified the cleavage sites in\u003cbr /\u003ethe extracellular juxtamembrane region of Ptprz by TACE and MMP-9. This is the\u003cbr /\u003efirst evidence of the metalloproteinase-mediated processing of an RPTP in the central\u003cbr /\u003enervous system. \u003cbr /\u003e I also identified the proteolytic processing of Ptprz by plasmin in the adult mouse\u003cbr /\u003ebrain, which is markedly enhanced after kainate-induced seizures. We estimated the\u003cbr /\u003ecleavage sites in the extracellular region of Ptprz based on cell-based assays and \u003ci\u003ein vitro\u003c/i\u003edigestion experiments with recombinant proteins. 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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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Item type | 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 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Proteolytic processing of protein tyrosine phosphatase receptor type Z in the CNS | |||||
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 | |||||
著者名 |
CHOW, PAKHONG Jeremy
× CHOW, PAKHONG Jeremy |
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フリガナ |
チョウ, パク ホンジェレミー
× チョウ, パク ホンジェレミー |
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著者 |
CHOW, PAKHONG Jeremy
× CHOW, PAKHONG Jeremy |
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学位授与機関 | ||||||
学位授与機関名 | 総合研究大学院大学 | |||||
学位名 | ||||||
学位名 | 博士(理学) | |||||
学位記番号 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 総研大甲第1204号 | |||||
研究科 | ||||||
値 | 生命科学研究科 | |||||
専攻 | ||||||
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 | ||||||
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 |