セルラー・クリーンアップ(Cellular Cleanup)

ad
ad
ad
ad
ad

アルツハイマー病の治療に役立つ新しい無膜オルガネラを発見、その特性を解明 Researchers discover and characterize a novel membraneless organelle that could play a role in Alzheimer’s treatment

2022-06-16 カリフォルニア大学サンタバーバラ校(UCSB)

これまで知られていなかった新しいオルガネラ(細胞内構造物)を発見した。このオルガネラの機能は、ストレス時に欠陥タンパク質を掃除し、細胞の機能を最高の状態に維持することである。BAG2凝縮体と名付けられたこの膜のないオルガネラを最適化することで、アルツハイマー病、パーキンソン病、その他の神経変性疾患など、誤ったタンパク質の形成に起因する疾患の治療法につながる可能性があります。

<関連情報>

ストレスがクライアントをBAG2ユビキチン非依存性分解コンデンセート経由でプロテアソームへ導く Stress routes clients to the proteasome via a BAG2 ubiquitin-independent degradation condensate

Daniel C. Carrettiero,Maria C. Almeida,Andrew P. Longhini,Jennifer N. Rauch,Dasol Han,Xuemei Zhang,Saeed Najafi,Jason E. Gestwicki & Kenneth S. Kosik
Nature Communications  Published:02 June 2022
DOI:https://doi.org/10.1038/s41467-022-30751-4

Abstract

The formation of membraneless organelles can be a proteotoxic stress control mechanism that locally condenses a set of components capable of mediating protein degradation decisions. The breadth of mechanisms by which cells respond to stressors and form specific functional types of membraneless organelles, is incompletely understood. We found that Bcl2-associated athanogene 2 (BAG2) marks a distinct phase-separated membraneless organelle, triggered by several forms of stress, particularly hyper-osmotic stress. Distinct from well-known condensates such as stress granules and processing bodies, BAG2-containing granules lack RNA, lack ubiquitin and promote client degradation in a ubiquitin-independent manner via the 20S proteasome. These organelles protect the viability of cells from stress and can traffic to the client protein, in the case of Tau protein, on the microtubule. Components of these ubiquitin-independent degradation organelles include the chaperone HSP-70 and the 20S proteasome activated by members of the PA28 (PMSE) family. BAG2 condensates did not co-localize with LAMP-1 or p62/SQSTM1. When the proteasome is inhibited, BAG2 condensates and the autophagy markers traffic to an aggresome-like structure.

タイトルとURLをコピーしました