Structural study of the association between the nuclear lamina and nuclear pore complexes

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K21178
• Project/Area Number (Other): 18H06045 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0701:Biology at molecular to cellular levels, and related fields
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: Shimi Takeshi 東京工業大学, 科学技術創成研究院, 特任准教授 (60817568)
• Project Period (FY): 2018-08-24 – 2021-03-31
• Keywords: Lamina / lamin / Nuclear pore complex / Nucleoporin / Laminopathies

Outline of Final Research Achievements

We analyzed the structural relationship between the lamina/lamin and the nuclear pore complex (NPC) in mouse embryonic fibroblasts (MEFs) using fluorescence three-dimensional structured illumination microscopy (3D-SIM) combined with computer-vision and cryo-electron tomography (cryo-ET). We showed that the NPC followed the perimeter of lamin fibers of the lamina, and the NPC was redistributed by Knockout of LA or LB1. Furthermore, Lamin filaments were structurally associated with the nucleoplasmic ring of the NPC. We also found that knockdown of a nucleoporin, ELYS altered the spatial relationship between the lamin fiber and the NPC. These results indicated that LA/C and LB1 are required for regulating the normal structure of the lamina and the NPC through ELYS. Our quantitative approach combining 3D-SIM and cryo-ET may shed light on the physiological properties of and pathological changes in lamin-NPC interactions.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

ラミンと核膜孔複合体の結合は、それぞれの構造と機能に働きかける局所場であり、本研究でこの結合について定量解析をおこなったことは、細胞生理学的な意義が極めて大きいと考えられる。今回の成果は今後、心筋症、筋ジストロフィー、早老症に代表される、ラミンの変異を原因とする遺伝病（ラミノパシー）の分子レベルでの解明につながると期待される。