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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...
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Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
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Eukaryotic cells have different motor proteins for transporting various cargo within the cell. These motor proteins differ based on the filament they associate with, the direction they move within the cell, and the type of cargo they transport. Motor proteins that associate with microtubules are known as microtubule-associated motor proteins. There are two families of microtubule-associated motor proteins —Kinesins and Dyneins. Both these proteins assist in the transport of cellular...
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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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Microtubules are dynamic structures that undergo continuous assembly and disassembly. They originate from specialized multi-protein complexes known as microtubule organizing centers or MTOCs. Within the MTOC, the point of origin of the microtubule is known as the minus end, while the end radiating outward is the plus end. Microtubules serve two primary functions — the organization of spindle complexes to separate sister chromatids during mitotic or meiotic cell division and the formation...
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ヴァソヒビンはチューブリン結合活性をコードする.

Joppe Nieuwenhuis1, Athanassios Adamopoulos1, Onno B Bleijerveld1

  • 1Division of Biochemistry, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands.

Science (New York, N.Y.)
|November 18, 2017
PubMed
まとめ

研究者は,微小管の異質性に影響を与える重要な翻訳後の改変であるチューブリンオキソシネーションを長らく探していた酵素としてワソヒビンを特定しました. この発見はチューブリンチロシネーションサイクルに光を当てます

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科学分野:

  • 細胞生物学
  • 分子生物学
  • 生物化学

背景:

  • 微小管は 細胞機能に不可欠なダイナミックなポリマーです
  • アルファチューブリンのオキシトシネーションを含む,微小管の異質性を生み出す.
  • チューブリン・オキシトシネーションを触媒する酵素は,何十年にもわたって特定されていなかった.

研究 の 目的:

  • チューブリン・オキシトシネーションの 難解な酵素を特定する
  • チューブリンチロシネーションサイクルを調節する分子メカニズムを解明する.

主な方法:

  • ヒトのハプロイド細胞の遺伝子検査で,チューブリンオキソシネーションのレギュレータを特定する.
  • 精製されたヴァソヒビンを用いた生化学分析
  • ヴァソヒビン (VASH1とVASH2) とSVBP機能の分析

主要な成果:

  • SVBPペプチドは,ヴァソヒビン (VASH1とVASH2) の豊富さを調節する.
  • ヴァソヒビンは,SVBP以外では,アルファチューブリン変異を有意に増加させた.
  • 精製されたヴァソヒビンは,アルファチューブリンのC端のチロシンを直接除去した.
  • ヴァソヒビンは,細胞型に依存する役割を持ち,細胞に追加的な detyrosinating 活動があります.

結論:

  • ヴァソヒビンは,チューブリンチロシネーションサイクルで欠けているリンクであり,主催性チロシネーション酵素として作用する.
  • この発見は血管新生の調節を超えて 既知のヴァソヒビンの機能を再定義します
  • 微小管のダイナミクスと細胞のプロセスを理解するには,チューブリンオキソシネーションを理解することが重要です.