PIGB maintains nuclear lamina organization in skeletal muscle of Drosophila

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06629
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44010:Cell biology-related
• Research Institution: Rikkyo University
• Principal Investigator: Yamamoto-hino Miki (日野美紀) 立教大学, 理学部, 特定課題研究員 (40301783)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 核ラミナ / ラミン / クロマチン / 核の脆弱性 / 核膜蛋白質 / 骨格筋

Outline of Final Research Achievements

The nuclear lamina (NL) plays various roles and participates in nuclear integrity, chromatin organization, and transcriptional regulation. Lamin proteins, the main components of the NL, form a homogeneous meshwork structure under the nuclear envelope. We found that PIGB, an enzyme involved in glycosylphosphatidylinositol (GPI) synthesis, is responsible for the homogeneous lamin meshwork in Drosophila. Loss of PIGB resulted in heterogeneous distributions of B-type lamin and lamin-binding proteins in larval muscles. These phenotypes were rescued by expression of PIGB lacking GPI synthesis activity. The PIGB mutant exhibited changes of lamina-associated domains that are large heterochromatic genomic regions in the NL and deformation of muscle fibers. These results suggest that PIGB maintains the homogeneous meshwork of the NL, which may be essential for chromatin distribution and nuclear mechanical properties.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

これまでにラミンの分布を制御する因子は見つかっておらず、PIGBは初めての報告である。ラミンが均一な網目構造をとることの意義は不明であったが、本研究によって、核膜蛋白質の正常な分布やクロマチンの構造の維持に必要であることを示すことができた。さらにその異常は核膜の堅牢性や遺伝子発現などにも影響を与え、ラミンの均一な網目構造は核が適切に機能を発揮するために重要であることが示唆された。さらに変異ラミンによって引き起こされる核膜病の理解に発展する可能性を示すことができた。