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Characterization of the interaction between Parkin and TSPO-VDAC complex in mediating immune responses in Drosophila

Title
Characterization of the interaction between Parkin and TSPO-VDAC complex in mediating immune responses in Drosophila
Translated Title
초파리 모델 시스템에서 파킨 단백질이 매개하는 감염과 상처 발생에 대한 생체 내 반응과 TSPO-VDAC 복합체의 상호작용
Authors
Cho, Jae Ho
DGIST Authors
Cho, Jae Ho; Lee, Sung Bae; Hong, Jae Sung
Advisor(s)
Lee, Sung Bae
Co-Advisor(s)
Hong, Jae Sung
Issue Date
2016
Available Date
2016-02-12
Degree Date
2016. 2
Type
Thesis
Keywords
Septic injuryWound선천성 면역 반응전염성 부상상처ParkinTSPOInnate immune responseVDAC (porin)
Abstract
Parkin, an E3 ubuquitin ligase associated with Parkinson's disease (PD), has recently been implicated in mediating innate immunity. However, molecular details regarding parkin-mediated immune response remain to be elucidated. Here, we identified mitochondrial TSPO-VDAC complex to genetically interact with parkin in mediating responses against infection and wound in Drosophila. The loss-of-function mutation in parkin results in defective immune response against bacterial infection. Additionally, parkin mutant larvae showed hypersensitivity against wound regardless of bacterial infection. Interestingly, the combinatorial trans-heterozygotic mutations in parkin and TSPO, or parkin and VDAC showed similar lethal tendency with parkin homozygous mutants. Furthermore, knockdown of TSPO alone also resulted in defective responses to infection and wound analogously to parkin mutants. Taken together, we propose that parkin cooperates with TSPO-VDAC complex to mediate responses against infection and wound. ⓒ 2016 DGIST
Table Of Contents
Ⅰ. INTRODUCTION 1 -- Ⅱ. MATERIALS AND METHOD 3 -- 2.1. Fly strains 3 -- 2.2. Prediction of transmembrane domain of dTSPO 3 -- 2.3. Infection and injury experiment 3 -- 2.4. Analysis of survival rate 4 -- 2.5. Single colony isolation of remaining bacteria inside the body after infection 4 -- 2.6. RNA extraction, cDNA synthesis, reverse transcription-PCR (RT-PCR) and quantitative PCR (qPCR) 5 -- Ⅲ. RESULT 6 -- 3.1. Parkin loss-of-function mutation induces defects in immune defense and wound repair 6 -- 3.2. Parkin and mitochondrial protein TSPO genetically interact in mediating immune response 8 -- 3.3. Loss of TSPO function shows similar defects to parkin mutants in responses to infection and wound 10 -- 3.4. Mitochondrial TSPO-VDAC complex is involved in parkin-mediated immune defense 12 -- IV. DISCUSSION 13 -- Figures 16 -- References 35 -- Summary in Korean 39
URI
http://dgist.dcollection.net/jsp/common/DcLoOrgPer.jsp?sItemId=000002229353
http://hdl.handle.net/20.500.11750/1470
DOI
10.22677/thesis.2229353
Degree
Master
Department
Brain and Cognitive Sciences
University
DGIST
Files:
Collection:
Brain and Cognitive SciencesThesesMaster


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