Molecular mechanism of selective autophagy against bacterial pathogens

• Project/Area Number: 26462776
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Kyoto University
• Principal Investigator: Nozawa Takashi 京都大学, 医学研究科, 助教 (10598858)
• Co-Investigator(Kenkyū-buntansha): 相川 知宏 京都大学, 医学研究科, 助教 (70725499)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: オートファジー / Rab GTPase / オートファジーアダプター / RAB GTPase / A群レンサ球菌 / Rabタンパク質

Outline of Final Research Achievements

We performed comprehensive analysis of Rab GTPase family proteins in autophagy against bacterial pathogens. We identified Rab35 as a novel autophagy regulator. Rab35 binds to NDP52 and regulates the recruitment of NDP52 to invading bacteria. We also found that NLRP4, intracellular pattern recognition receptor, is recruited to invaded bacteria and regulates Rho signaling via RhoGDI to promote the fusion between recycling endosomes and autophagosomes. The fusion step is required for the extension of autophagosome membranes and form complete autophagosomes. Taken together, we revealed how host cells recognize pathogens and induce selective autophagy.

Research Products

• [Journal Article] YvqE and CovRS of Group A Streptococcus Play a Pivotal Role in Viability and Phenotypic Adaptations to Multiple Environmental Stresses (2017)
  • Author(s): Roobthaisong A, Aikawa C,Nozawa T, Maruyama F, Nakagawa I
  • Journal Title: Plos One Volume: 12 Issue: 1 Pages: e0170612-e0170612
  • DOI: 10.1371/journal.pone.0170612
  • NAID: 120005980868
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Bcl-xL Affects Group A Streptococcus-Induced Autophagy Directly, by Inhibiting Fusion between Autophagosomes and Lysosomes, and Indirectly, by Inhibiting Bacterial Internalization via Interaction with Beclin 1-UVRAG (2017)
  • Author(s): Nakajima S, Aikawa C, Nozawa, T, Minowa-Nozawa A, Toh H, Nakagawa I
  • Journal Title: PLos One Volume: 12 Issue: 1 Pages: e0170138-e0170138
  • DOI: 10.1371/journal.pone.0170138
  • NAID: 120005971033
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The STX6-VTI1B-VAMP3 complex facilitates xenophagy by regulating the fusion between recycling endosomes and autophagosomes (2017)
  • Author(s): T. Nozawa, A. Minowa-Nozawa, C. Aikawa, I. Nakagawa.
  • Journal Title: Autophagy Volume: 13 Issue: 1 Pages: 57-69
  • DOI: 10.1080/15548627.2016.1241924
  • NAID: 120006337978
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A locus encoding variable defence systems against invading DNA identified in Streptococcus suis. (2017)
  • Author(s): Okura M, Nozawa T, Watanabe T, Murase K, Nakagawa I, Takamatsu D, Osaki M, Sekizaki T, Gottschalk M, Hamada S, Maruyama F.
  • Journal Title: Genome Biol Evol Volume: 9 Issue: 4 Pages: 1000-1012
  • DOI: 10.1093/gbe/evx062
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] DNA-based culture-independent analysis detects the presence of group a streptococcus in throat samples from healthy adults in Japan. (2016)
  • Author(s): T. Kulkarni, C. Aikawa, T. Nozawa, K. Murase, *F. Maruyama, I. Nakagawa.
  • Journal Title: BMC Microbiol. Volume: 16 Pages: 237-237
  • NAID: 120006223635
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Golgi-Resident GTPase Rab30 Promotes the Biogenesis of Pathogen-Containing Autophagosomes. (2016)
  • Author(s): Oda S, Nozawa T, Nozawa-Minowa A, Tanaka M, Aikawa C, Harada H, Nakagawa I.
  • Journal Title: PLoS One Volume: 11 Issue: 1 Pages: e0147061-e0147061
  • DOI: 10.1371/journal.pone.0147061
  • NAID: 120005743648
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Rab17-mediated recycling endosomes contribute to autophagosome formation in response to Group A Streptococcus invasion. (2014)
  • Author(s): B. Haobam, T. Nozawa, A. Minowa-Nozawa, M. Tanaka, S. Oda, T. Watanabe, C. Aikawa, F. Maruyama, I. Nakagawa.
  • Journal Title: Cellular Microbiology Volume: 16 Issue: 12 Pages: 1806-1821
  • DOI: 10.1111/cmi.12329
  • Peer Reviewed / Open Access
• [Presentation] ゼノファジーにおけるオートファジーアダプタータンパク質の時空間制御メカニズム (2017)
  • Author(s): 野澤孝志、野澤敦子、中川一路
  • Organizer: 第90回日本細菌学会総会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2017-03-19
  • Invited
• [Presentation] A Disrupted PI4P-Enriched TGN Induced by Group A Streptococcus Contributes to Xenophagy (2016)
  • Author(s): 野澤孝志、野澤敦子、中川一路
  • Organizer: 第89回日本細菌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2016-03-23
• [Presentation] Rab17-mediated recycling endosomes contribute to antibacterial autophagosome formation (2015)
  • Author(s): 野澤孝志
  • Organizer: 第88回 日本細菌学会総会
  • Place of Presentation: 岐阜
  • Year and Date: 2015-03-26 – 2015-03-29
• [Book] Autophagy, Infection, and the Immune Response (2014)
  • Author(s): T. Nozawa, I. Nakagawa
  • Total Pages: 352
  • Publisher: Wiley
• [Remarks] 京都大学 大学院医学研究科 微生物感染症学分野
  • URL: http://www.bac.med.kyoto-u.ac.jp/
• [Remarks] 京都大学大学院医学研究科微生物感染症学分野
  • URL: http://www.bac.med.kyoto-u.ac.jp/
• [Remarks] 東京医科歯科大学 テニュアトラックプログラム 野澤孝志
  • URL: http://www.tmd.ac.jp/cmn/tenu/program/no1_nozawa.html