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著作: [東尾 浩典]/[西村 範行]/Ishizaki Hiroyoshi/Miyoshi Jun/[織田 聡]/[坂根 亜由子]/[佐々木 卓也]/Doc2α and Munc13-4 Regulate Ca2+-Dependent Secretory Lysosome Exocytosis in Mast Cells./[The Journal of Immunology]

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LastModified
2013年11月27日(水) 14:46:57
Operator
三木 ちひろ
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佐々木 卓也
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種別 必須 学術論文(審査論文)
言語 必須 英語
招待 推奨
審査 推奨
カテゴリ 推奨
共著種別 推奨
学究種別 推奨
組織 推奨
著者 必須
  1. 東尾 浩典
    役割 任意
    貢献度 任意
    学籍番号 推奨
  2. 西村 範行
    役割 任意
    貢献度 任意
    学籍番号 推奨
  3. (英) Ishizaki Hiroyoshi
    役割 任意
    貢献度 任意
    学籍番号 推奨
  4. (英) Miyoshi Jun
    役割 任意
    貢献度 任意
    学籍番号 推奨
  5. 織田 聡
    役割 任意
    貢献度 任意
    学籍番号 推奨
  6. 坂根 亜由子([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.生理系.生化学])
    役割 任意
    貢献度 任意
    学籍番号 推奨
  7. 佐々木 卓也([徳島大学])
    役割 任意
    貢献度 任意
    学籍番号 推奨
題名 必須

(英) Doc2α and Munc13-4 Regulate Ca2+-Dependent Secretory Lysosome Exocytosis in Mast Cells.

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(英) The Doc2 family comprises the brain-specific Doc2alpha and the ubiquitous Doc2beta and Doc2gamma. With the exception of Doc2gamma, these proteins exhibit Ca(2+)-dependent phospholipid-binding activity in their Ca(2+)-binding C2A domain and are thought to be important for Ca(2+)-dependent regulated exocytosis. In excitatory neurons, Doc2alpha interacts with Munc13-1, a member of the Munc13 family, through its N-terminal Munc13-1-interacting domain and the Doc2alpha-Munc13-1 system is implicated in Ca(2+)-dependent synaptic vesicle exocytosis. The Munc13 family comprises the brain-specific Munc13-1, Munc13-2, and Munc13-3, and the non-neuronal Munc13-4. We previously showed that Munc13-4 is involved in Ca(2+)-dependent secretory lysosome exocytosis in mast cells, but the involvement of Doc2 in this process is not determined. In the present study, we found that Doc2alpha but not Doc2beta was endogenously expressed in the RBL-2H3 mast cell line. Doc2alpha colocalized with Munc13-4 on secretory lysosomes, and interacted with Munc13-4 through its two regions, the N terminus containing the Munc13-1-interacting domain and the C terminus containing the Ca(2+)-binding C2B domain. In RBL-2H3 cells, Ca(2+)-dependent secretory lysosome exocytosis was inhibited by expression of the Doc2alpha mutant lacking either of the Munc13-4-binding regions and the inhibition was suppressed by coexpression of Munc13-4. Knockdown of endogenous Doc2alpha also reduced Ca(2+)-dependent secretory lysosome exocytosis, which was rescued by re-expression of human Doc2alpha but not by its mutant that could not bind to Munc13-4. Moreover, Ca(2+)-dependent secretory lysosome exocytosis was severely reduced in bone marrow-derived mast cells from Doc2alpha knockout mice. These results suggest that the Doc2alpha-Muunc13-4 system regulates Ca(2+)-dependent secretory lysosome exocytosis in mast cells.

キーワード 推奨
  1. (英) Animals
  2. (英) Antigens
  3. (英) Bone Marrow
  4. カルシウム(calcium)
  5. (英) Calcium-Binding Proteins
  6. (英) Cell Line
  7. (英) Cercopithecus aethiops
  8. (英) Exocytosis
  9. (英) Gene Expression Regulation
  10. (英) Humans
  11. (英) Ionophores
  12. (英) Lysosomes
  13. (英) Mast Cells
  14. (英) Membrane Proteins
  15. (英) Mice
  16. (英) Nerve Tissue Proteins
  17. (英) Phorbol Esters
  18. (英) Protein Binding
  19. (英) Rats
発行所 推奨
誌名 必須 The Journal of Immunology([The American Association of Immunologists])
(pISSN: 0022-1767, eISSN: 1550-6606)
ISSN 任意 0022-1767
ISSN: 0022-1767 (pISSN: 0022-1767, eISSN: 1550-6606)
Title: Journal of immunology (Baltimore, Md. : 1950)
Title(ISO): J Immunol
Publisher: American Association of Immunologists
 (NLM Catalog  (Scopus  (CrossRef (Scopus information is found. [need login])
必須 180
必須 7
必須 4774 4784
都市 任意
年月日 必須 2008年 4月 1日
URL 任意
DOI 任意
PMID 任意 18354201    (→Scopusで検索)
NAID 任意
WOS 任意 000257506700050
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評価値 任意
被引用数 任意
指導教員 推奨
備考 任意
  1. (英) Article.Affiliation: Department of Biochemistry, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.

  2. (英) Article.PublicationTypeList.PublicationType: Journal Article

  3. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't