タンパク質凝集の主要因として細胞内極性を特定 (Scientists Identify Subcellular Polarity as Key Factor in Protein Aggregation)

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2026-03-08 中国科学院(CAS)

中国学院生物物理研究所WANG Lei研究チームは、細胞器官極性(polarity)分子混雑定量測定し、タンパク質凝集関係明らかした。極性応答プローブHaloタンパク質細胞区画局在せ、細胞環境比較した結果、体(ER)内部細胞質より高い極性高い分子混雑持つこと判明した。また、ハンチンチン遺伝子由来polyQタンパク質は、極性高いERでは凝集にくいことた。処理により極性低下すると凝集増加したことから、タンパク質凝集分子混雑より極性重要要因ある可能性示唆た。研究は、タンパク質恒常神経変性疾患理解新た視点提供する。

タンパク質凝集の主要因として細胞内極性を特定 (Scientists Identify Subcellular Polarity as Key Factor in Protein Aggregation)
Schematic diagram of the model for polarity-regulated protein condensate and aggregate formation (Image by WANG Lei’s group)

<関連情報>

ヒト細胞において、小胞体は高い極性を示し、タンパク質凝集は少ない The endoplasmic reticulum displays high polarity with low protein aggregation in human cells

Xinwei Hu,Junlin Chen,Ping Liu,Huaiyue Zhang,Yu Liu,Xin Zhang & Lei Wang
Communications Biology  Published:03 February 2026
DOI:https://doi.org/10.1038/s42003-025-09491-w

Abstract

Many physicochemical properties in the cellular milieu are important for cell function and survival. However, the polarity of different subcellular compartments and its role in protein condensate and aggregate formation within cells are less characterized. Here, we develop a method to compare the polarity in different subcellular compartments using the same polarity-sensitive solvatochromic fluorescent probe. Unexpectedly, the endoplasmic reticulum (ER) lumen displays a higher polarity and a more crowded environment than the cytosol in human cells. Polarity-decreasing and crowding-increasing hypertonic conditions induce condensate or aggregate formation of two intrinsically disordered proteins, with-no-lysine kinase 1 and Huntingtin gene (Htt) exon1 with an expanded polyQ stretch (Htt-polyQ), in the cytosol. However, targeting Htt-polyQ to the ER prevents its aggregation, suggesting that polarity but not crowding is more relevant to protein aggregation. Our results reveal the heterogeneity in subcellular polarity and crowding, and uncover previously unrecognized high-polarity in the ER lumen, which provides a unique environment for maintaining robust proteostasis.

生物化学工学
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