2017 Fiscal Year Final Research Report
Elucidation of the molecular mechanism of Rab35-activation-dependent neurite outgrowth
| Project/Area Number |
15H04367
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | 低分子量G蛋白質Rab / 神経突起伸長 / 小胞輸送 / 神経成長因子 / スクリーニング / Rabカスケード / Rabエフェクター / グアニンヌクレオチド交換因子 |
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| Outline of Final Research Achievements |
Neurite outgrowth, which is a prerequisite for neuronal network formation, requires massive addition of proteins and lipids to the tips of growing neurites by membrane trafficking. Accumulating evidence has suggested that several Rab small GTPases such as Rab8 and Rab35 on recycling endosomes promote neurite outgrowth, but their regulatory mechanisms during neurite outgrowth are poorly understood. In this study, we identified DENND1A as a Rab35-GEF and Rabin8 as a Rab8-GEF and found that both GEFs are required for neurite outgrowth of PC12 cells. Knockdown of Rabin8 resulted in inhibition of neurite outgrowth, whereas its overexpression promoted it. We also found that Rabin8 is recruited to recycling endosomes in a Rab11-dependent manner and that it activates Rab8 and Rab10 there during neurite outgrowth. Furthermore, we comprehensively screened TBC proteins/Rab-GAPs and Rabs and succeeded in identifying TBC1D12 and Rab20 as novel negative regulators of neurite outgrowth.
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| Free Research Field |
細胞生物学
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