タウタンパク質が欠けているマウスの小口径アクソンにおけるマイクロチューブル組織の変化
1Department of Anatomy and Cell Biology, School of Medicine, University of Tokyo, Japan.
Nature
|June 9, 1994
まとめ
タウ遺伝子が欠けているマウスは,正常な神経系と軸索の延長を示した. しかし,タウの欠乏は微小管の安定性を低下させ,小さな軸索の組織を変化させ,タウは微小管の安定化に不可欠であり,延長ではないことを示唆しています.
科学分野:
- 神経科学は神経科学である.
- 細胞生物学 細胞生物学
- 遺伝学 遺伝学とは
背景:
- タウタンパク質は,重要なニューロンマイクロチューブル関連タンパク質である.
- タウは,神経細胞の形態変異,特に軸索の伸びと維持に不可欠であると信じられています.
- その提案された機能には,軸索のマイクロチューブルを横断橋渡しし,チューブリンポリメリゼーションを促進する機能が含まれています.
研究 の 目的:
- タウ遺伝子の役割を in vivo で調査する.
- タウが軸索の伸びと維持に不可欠であるという仮説を検証する.
- 神経細胞の構造と発達におけるタウの特定の機能を明らかにする.
主な方法:
- 遺伝子ターゲティングは,タウ欠乏症のマウスを生み出すために使われました.
- タウ欠乏マウスの神経系の免疫組織学的分析.
- タウ欠乏性マウスの培養ニューロンにおける軸索の伸びと微小管の組織の評価.
主要な成果:
- タウ欠乏症のマウスは,免疫組織学的に正常な神経系の発達を示した.
- 培養ニューロンの軸索延長は,タウの欠如によって有意に影響されませんでした.
- 微小管の安定性の低下と組織の変化は,小口径の軸索で観察されました.
- マイクロチューブル関連タンパク質1Aのレベルが上昇し,大口径アクソンにおけるタウの機能を補う可能性があることが示されました.
結論:
- この研究は,軸索延伸におけるタウの役割に関する提案に異議を唱えている.
- タウは,特に特定の軸索型における軸索微小管の安定化と組織化において極めて重要であることが確認されています.
- 微小管に関連した他のタンパク質を含む補償機構は,大口径の軸索に存在する可能性があります.
さらに関連する動画
07:21Quantitative Microtubule Fractionation Technique to Separate Stable Microtubules, Labile Microtubules, and Free Tubulin in Mouse Tissues
Published on: November 17, 2023
10:38Using Live-Cell Imaging to Measure the Effects of Pathological Proteins on Axonal Transport in Primary Hippocampal Neurons
Published on: December 22, 2023
関連する概念動画
01:18Microtubules
Microtubules are the thickest cytoskeletal filaments with a diameter of 25 nm. In prokaryotic organisms, microtubules are commonly found in locomotory appendages like cilia and flagella. In eukaryotic cells, microtubules form specialized extensions for moving fluid over the surface, like those found in cells lining the intestine.
Microtubules have two structurally similar globular protein subunits: α and β tubulins. In the cytosol, the α and β tubulins form a heterodimer. These αβ-heterodimers...
Microtubules have two structurally similar globular protein subunits: α and β tubulins. In the cytosol, the α and β tubulins form a heterodimer. These αβ-heterodimers...
01:42Microtubule Associated Proteins (MAPs)
Microtubule function and architecture are regulated by an array of specialized proteins called microtubule-associated proteins or MAPs. These proteins are widespread across different organisms and have conserved protein motifs, like the multi-TOG domain for tubulin binding found in the CLASP family of MAPs. Some MAPs are lineage-specific based on their conserved domains. Their functions depend upon the cytoskeletal architecture and cell type they are located within. In-plant cells, a specific...
01:45Destabilization of Microtubules
The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
01:32Assembly of Complex Microtubule Structures
Complex microtubule structures are present in resting cells and in dividing cells. In resting cells, they are responsible for maintaining the cellular architecture, tracks for intracellular transport, positioning of organelles, assembly of cilia and flagella. They mediate the bipolar spindle assembly for chromosomal segregation and positioning of the cell division plate in dividing cells. The formation of microtubule complex structures depends on the cell type, cell stage, and cell function.
01:15Drugs that Stabilize Microtubules
Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
02:17Microtubule Instability
Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated assembly and...