{"created":"2023-06-20T13:20:59.550844+00:00","id":1070,"links":{},"metadata":{"_buckets":{"deposit":"9cd9347d-a021-4949-b889-c81c7a5c0b2a"},"_deposit":{"created_by":1,"id":"1070","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"1070"},"status":"published"},"_oai":{"id":"oai:ir.soken.ac.jp:00001070","sets":["2:430:21"]},"author_link":["0","0","0"],"item_1_creator_2":{"attribute_name":"著者名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"CHOW, PAKHONG Jeremy"}],"nameIdentifiers":[{}]}]},"item_1_creator_3":{"attribute_name":"フリガナ","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"チョウ, パク ホンジェレミー"}],"nameIdentifiers":[{}]}]},"item_1_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2008-09-30"}]},"item_1_degree_grantor_5":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"総合研究大学院大学"}]}]},"item_1_degree_name_6":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（理学）"}]},"item_1_description_12":{"attribute_name":"要旨","attribute_value_mlt":[{"subitem_description":"Protein tyrosine phosphatase receptor type Z (Ptprz, also known as PTPζ or RPTPβ) is
preferentially expressed in the brain as a major chondroitin sulfate proteoglycan.
Three splicing variants, two receptor-type isoforms and one secretory isoform, are
known. Ptprz interacts with the PSD95 family through its intracellular
carboxyl-terminal PDZ-binding motif in the postsynaptic density of the adult brain.
Ptprz>-deficient mice display impairments in spatial and contextual learning. Here, I
show that the extracellular region of the receptor isoforms of Ptprz are cleaved by
metalloproteinases including ADAM-17 (TACE) and subsequently the
membrane-tethered fragment is cleaved by presenilin/γ-secretase, releasing its
intracellular region into the cytoplasm: Noteworthily, the intracellular fragment of
Ptprz shows nuclear localization. Administration of GM6001, an inhibitor of
metalloproteinases, to mice demonstrated the metalloproteinase-mediated cleavage of
Ptprz under physiological conditions. Furthermore, I identified the cleavage sites in
the extracellular juxtamembrane region of Ptprz by TACE and MMP-9. This is the
first evidence of the metalloproteinase-mediated processing of an RPTP in the central
nervous system.
I also identified the proteolytic processing of Ptprz by plasmin in the adult mouse
brain, which is markedly enhanced after kainate-induced seizures. We estimated the
cleavage sites in the extracellular region of Ptprz based on cell-based assays and in vitrodigestion experiments with recombinant proteins. The findings indicate that Ptprz is a
physiological target for activity-dependent proteolytic processing by the tPA/plasmin
system, and suggest that the proteolytic fragments are involved in the structural and
functional processes of the synapses during learning and memory.
","subitem_description_type":"Other"}]},"item_1_description_18":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"}]},"item_1_description_7":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_description":"総研大甲第1204号","subitem_description_type":"Other"}]},"item_1_select_14":{"attribute_name":"所蔵","attribute_value_mlt":[{"subitem_select_item":"有"}]},"item_1_select_8":{"attribute_name":"研究科","attribute_value_mlt":[{"subitem_select_item":"生命科学研究科"}]},"item_1_select_9":{"attribute_name":"専攻","attribute_value_mlt":[{"subitem_select_item":"19 基礎生物学専攻"}]},"item_1_text_10":{"attribute_name":"学位授与年度","attribute_value_mlt":[{"subitem_text_value":"2008"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"CHOW, PAKHONG Jeremy","creatorNameLang":"en"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2016-02-17"}],"displaytype":"simple","filename":"甲1204_要旨.pdf","filesize":[{"value":"186.0 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"要旨・審査要旨","url":"https://ir.soken.ac.jp/record/1070/files/甲1204_要旨.pdf"},"version_id":"e5604c9c-3cc2-4d00-84cd-5dc1da540274"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2016-02-17"}],"displaytype":"simple","filename":"甲1204_本文.pdf","filesize":[{"value":"10.0 MB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"本文","url":"https://ir.soken.ac.jp/record/1070/files/甲1204_本文.pdf"},"version_id":"ef6f1743-1cbf-4a1e-a520-480529385c2c"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"thesis","resourceuri":"http://purl.org/coar/resource_type/c_46ec"}]},"item_title":"Proteolytic processing of protein tyrosine phosphatase receptor type Z in the CNS","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Proteolytic processing of protein tyrosine phosphatase receptor type Z in the CNS"},{"subitem_title":"Proteolytic processing of protein tyrosine phosphatase receptor type Z in the CNS","subitem_title_language":"en"}]},"item_type_id":"1","owner":"1","path":["21"],"pubdate":{"attribute_name":"公開日","attribute_value":"2010-02-22"},"publish_date":"2010-02-22","publish_status":"0","recid":"1070","relation_version_is_last":true,"title":["Proteolytic processing of protein tyrosine phosphatase receptor type Z in the CNS"],"weko_creator_id":"1","weko_shared_id":1},"updated":"2023-06-20T15:49:52.962420+00:00"}