Disruption of cell polarity influences the secretion of gastrointestinal hormones

• Project/Area Number: 25460269
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Takarazuka University of Medical and Health Care
• Principal Investigator: HARADA Reiko 宝塚医療大学, 保健医療学部, 教授 (40230718)
• Co-Investigator(Kenkyū-buntansha): KUNII Masataka 大阪大学, 大学院医学系研究科, 助教 (80614768)
• Co-Investigator(Renkei-kenkyūsha): HARADA Akihiro 大阪大学, 大学院医学系研究科, 教授 (40251441)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 細胞極性 / 消化管ホルモン / ノックアウトマウス / インクレチン / rab8

Outline of Final Research Achievements

Using mice deficient in the small GTP-binding protein Rab8a, we demonstrated that rab8a is responsible for the localization of apical proteins such as SGLT in intestinal epithelial cells. Rab8a knockout mice showed increased GLP-1 expression and co-expression of GLP-1and Chromogranin A, but the subcellular localization of GLP-1 was not affected.
We therefore tried to generate knockout mice in which the localization of basolateral proteins is disrupted. However in all the knockout mice we analyzed, there were no obvious missorting of basolateral proteins. On the other hand, mice deficient in SNAP23 showed difference in hormone secretion, and this result is now under submission.

Research Products

• [Journal Article] EHBP1L1 coordinates Rab8 and Bin1 to regulate apical-directed transport in polarized epithelial cells. (2016)
  • Author(s): Nakajo A, Yoshimura SI, Togawa H, Kunii M, Iwano T, Izumi A, Noguchi Y, Watanabe A, Goto A, Sato T, Harada A.
  • Journal Title: Journal of Cell Biology Volume: 212 Issue: 3 Pages: 297-306
  • DOI: 10.1083/jcb.201508086
  • Peer Reviewed / Open Access
• [Journal Article] Rab8a vesicles regulate Wnt ligand delivery and Paneth cell maturation at the intestinal stem cell niche. (2015)
  • Author(s): Das S, Yu S, Sakamori R, Vedula P, Feng Q, Flores J, Hoffman A, Fu J, Stypulkowski E, Rodriguez A, Dobrowolski R, Harada A, Hsu W, Bonder EM, Verzi MP, Gao N
  • Journal Title: Development Volume: 142(12) Issue: 12 Pages: 2147-2162
  • DOI: 10.1242/dev.121046
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Functional redundancy of protein kinase D1 and protein kinase D2 in neuronal polarity. (2015)
  • Author(s): Avriyanti E, Atik N, Kunii M, Furumoto N, Iwano T, Yoshimura S, Harada R, Harada A.
  • Journal Title: Neuroscience Research Volume: 95 Pages: 12-20
  • DOI: 10.1016/j.neures.2015.01.007
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Rab11a is required for apical protein localisation in the intestine. (2014)
  • Author(s): Sobajima T, Yoshimura S, Iwano T, Kunii M, Watanabe M, Atik N, Mushiake S, Morii E, Koyama Y, Miyoshi E, Harada A
  • Journal Title: Biol Open Volume: 4 Issue: 1 Pages: 86-94
  • DOI: 10.1242/bio.20148532
  • Peer Reviewed / Open Access
• [Journal Article] The Role of PKD in Cell Polarity, Biosynthetic Pathways, and Organelle/F-actin Distribution (2014)
  • Author(s): Nur Atik他
  • Journal Title: Cell Structure and Function Volume: 39 Issue: 1 Pages: 61-77
  • DOI: 10.1247/csf.13020
  • NAID: 130004137601
  • ISSN: 0386-7196, 1347-3700
  • Peer Reviewed
• [Journal Article] Rab8a and Rab8b are essential for multiple apical transport pathways but insufficient for ciliogenesis. (2013)
  • Author(s): Sato T, Iwano T, Kunii M, Matsuda S, Mizoguchi R, Jung Y, Hagiwara H, Yoshihara Y, Yuzaki M, Harada R, Harada A.
  • Journal Title: J Cell Sci. Volume: 15;127(Pt 2) Pages: 422-31
  • DOI: 10.1242/jcs.136903
  • Peer Reviewed / Open Access
• [Presentation] 大脳皮質におけるSNARE分子の機能の解析 (2016)
  • Author(s): 國井政孝、原田彰宏
  • Organizer: 第121回日本解剖学会総会全国学術集会
  • Place of Presentation: ビッグパレット福島
  • Year and Date: 2016-03-29
• [Presentation] 細胞内極性輸送と繊毛形成におけるRab8a, bの協調的機能の解明 (2016)
  • Author(s): 佐藤隆史、岩野智彦、國井政孝、松田信爾、水口留美子、Yongwook Jung、萩原治夫、吉原吉浩、柚崎通介、原田玲子、原田彰宏
  • Organizer: 第121回日本解剖学会総会全国学術集会
  • Place of Presentation: ビッグパレット福島
  • Year and Date: 2016-03-29
• [Presentation] In vivo functions of genes involved in polarized transport (2015)
  • Author(s): Akihiro Harada
  • Organizer: American Society for Cell Biology (ASCB)
  • Place of Presentation: San Diego Convention Center, San Diego (USA)
  • Year and Date: 2015-12-15
  • Int'l Joint Research
• [Presentation] 細胞内極性輸送を司る遺伝子のin vivoにおける機能 (2015)
  • Author(s): 原田彰宏
  • Organizer: BMB2015
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-02
• [Presentation] Functions of genes involved in polarized transport in neuronal polarity (2015)
  • Author(s): Akihiro Harada
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸コンベンションセンター
  • Year and Date: 2015-07-29
• [Presentation] Rab11aは小腸においてapical腸タンパク質の局在を制御する (2015)
  • Author(s): 傍嶋智明、吉村信一郎、岩野智彦、國井政孝、渡辺雅彦、Nur Atik、虫明聡太郎、森井英一、小山佳久、三善英知、原田彰宏
  • Organizer: 第67回細胞生物学会大会
  • Place of Presentation: タワーホール船堀
  • Year and Date: 2015-07-01
• [Presentation] VAMP7はオートファジーによるミトコンドリア恒常性維持機構を介して膵β細胞からの第2相インスリン分泌を制御する (2015)
  • Author(s): 青柳共太、今泉美佳、板倉誠、鳥居征司、岸本琢磨、西脇知世乃、中道洋子、秋元義弘、原田彰宏、高橋正身、永松信哉
  • Organizer: 第67回細胞生物学会大会
  • Place of Presentation: タワーホール船堀
  • Year and Date: 2015-06-30
• [Book] やさしい自律神経生理学―命を支える仕組み (2015)
  • Author(s): 鈴木 郁子、内田 さえ、鍵谷 方子、原田 玲子
  • Total Pages: 248
  • Publisher: 中外医学社
• [Remarks] 大阪大学大学院 医学系研究科 細胞生物学
  • URL: http://www.med.osaka-u.ac.jp/pub/acb/index.html
• [Remarks] http://www.med.osaka-u.ac.jp/pub/acb/index.html
• [Remarks] http://www.med.osaka-u.ac.jp/pub/acb/index.html