2019 Fiscal Year Research-status Report
Role of kinesin/dynein adaptor JSAP in reactive oxygen species-induced cell death and lysosome positioning
| Project/Area Number |
19K16737
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| Research Institution | Kanazawa University |
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Principal Investigator |
I・KETUT GUNARTA 金沢大学, がん進展制御研究所, 助教 (90838393)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | JSAP / JLP / JSAP1 / Curcumin / Autophagy / Lysosome |
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| Outline of Annual Research Achievements |
Cell executes autophagy as a survival system under oxidative stress and the process of autophagy is tightly linked to the activity and the position of the lysosome. Here I will investigate the relationship between JSAP-mediated lysosome trafficking and cell death under acute oxidative stress condition. This study would contribute to the development of a novel therapeutic strategy for cancer. The results of our research in FY 2019 are: (1) We established the role of JLP in curcumin-induced cell death. JLP protect cell from curcumin-induced cell death by mediating autophagosome-lysosome fusion and activation of p38 MAPK.(2) The kinesin-1 heavy chain binding domain (KBD) but not dynactin p150Glued binding domain (DBD) of JLP is required for the regulation of lysosome traficking and autophagy.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
In order to analyze the role of JSAPs in lysosome positioning, JLP or JSAP1 knockdown cells were prepared. While JLP knockdown on cells give an expected phenotype, i.e. impairment of retrograde trafficking of lysosome, JSAP1 knockdown gives a different phenotype. Furthermore, sensitivity of JLP or JSAP1 knockdown cell toward curcumin-induced cell death were similar. This may suggest JLP and JSAP1, despite a high sequence homology, plays a different role in lysosome trafficking.
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| Strategy for Future Research Activity |
For future analysis of JSAPs-dependent lysosome trafficking, we will elucidate how the involvement of JSAP1 in the lysosome trafficking. For this purpose, knockdown and Crispr/Cas9-mediated knockout of JSAP1 gene in the cell model will be generated. Rescue experiment will be done in order to understand the function of JSAP1 in lysosome trafficking, autophagy and curcumin-induced cell death. By understanding the role of the two protein, we may able to clarify how lysosome trafficking is regulated under certain context.
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Research Products
(5 results)
