Tau contributes to the precise segregation of chromosomes by regulating katanin

2014 Fiscal Year Final Research Report

• Project/Area Number: 24791987
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Functional basic dentistry
• Research Institution: The Nippon Dental University
• Principal Investigator: HARUKA Sudo 日本歯科大学, 生命歯学部, 講師 (20372980)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 染色体不安定性 / タウ / 乳癌 / 微小管切断 / 紡錘体

Outline of Final Research Achievements

Regarding katanin-like (KL) and tau, I obtained data: 1) Human breast cancer derived mutant KL expressing RFL6 rat fibroblasts showed significant transformation, which was suppressed by expression of tau. In RFL6 cells, KL- induced loss of microtubules was inhibited by tau. 2) Exogenously KL expressing RFL6 cells showed chromosome missegregation and micronuclei formation. 3) In primary human mammary epithelial cells (HMECs), both endogenous tau and KL proteins localized on mitotic spindles. 4) Tau-knocked down(kd) HMECs showed a) alterations in kinetochore fibers, b) missegregation of chromosomes, and c) formation of micronuclei, some of which were inhibited by KL knockdown. 5) The isolated mitotic spindles from tau-kd HMECs showed physical fragility. 6) Tau-kd HMECs showed a) disconnected chromosomes to spindles and b) aneuploidy under p53 knockdown. These data support the hypothesis that tau contributes to precise chromosome segregation via inhibition of microtubule severing by KL.

Free Research Field

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