| Item type |
学位論文 / Thesis or Dissertation(1) |
| 公開日 |
2010-02-22 |
| タイトル |
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|
タイトル |
Proteolytic processing of protein tyrosine phosphatase receptor type Z in the CNS |
| タイトル |
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|
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 |
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|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_46ec |
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資源タイプ |
thesis |
| 著者名 |
CHOW, PAKHONG Jeremy
|
| フリガナ |
チョウ, パク ホンジェレミー
|
| 著者 |
CHOW, PAKHONG Jeremy
|
| 学位授与機関 |
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学位授与機関名 |
総合研究大学院大学 |
| 学位名 |
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学位名 |
博士（理学） |
| 学位記番号 |
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内容記述タイプ |
Other |
|
内容記述 |
総研大甲第1204号 |
| 研究科 |
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|
値 |
生命科学研究科 |
| 専攻 |
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|
値 |
19 基礎生物学専攻 |
| 学位授与年月日 |
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学位授与年月日 |
2008-09-30 |
| 学位授与年度 |
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値 |
2008 |
| 要旨 |
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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 |
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値 |
有 |
| フォーマット |
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内容記述タイプ |
Other |
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内容記述 |
application/pdf |
要旨・審査要旨 (186.0 kB)
