細胞小器官の構造と機能を解明する新しいモデル(New Model Brings Insight to Cell Organelle’s Structure and Function)

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2024-10-28 カリフォルニア大学サンディエゴ校(UCSD)

カリフォルニア大学サンディエゴ校の研究チームは、細胞内でタンパク質や脂質の輸送を担う小胞体(ER)の構造と動態を示す物理モデルを開発しました。このモデルは、ERが張力と引っ張り力のバランスで形成され、急速に再編される「活性液体ネットワーク」として機能する仕組みを明らかにし、神経疾患に関連するER構造異常の理解を深めることに寄与しています。

<関連情報>

活動的な液体ネットワークとしての小胞体 The endoplasmic reticulum as an active liquid network

Zubenelgenubi C. Scott, Samuel B. Steen, Greg Huber, +1, and Elena F. Koslover
Proceedings of the National Academy of Sciences  Published:October 11, 2024
DOI:https://doi.org/10.1073/pnas.2409755121

細胞小器官の構造と機能を解明する新しいモデル(New Model Brings Insight to Cell Organelle’s Structure and Function)

Significance

The peripheral endoplasmic reticulum (ER) forms a continuous, dynamic network of tubules that plays an important role in protein sorting, export and quality control, cellular signaling, and stress response. Elucidating how the unique morphology of the ER arises and supports its function is critical to developing a mechanistic understanding of the many neurological diseases associated with ER structural perturbations. We develop a physical model of the ER as an active liquid network, revealing how its cellular-scale structure emerges from small-scale dynamic rearrangements. The model demonstrates how key features of ER architecture can arise from a balance of tubule growth and tension-driven sliding. This work provides insight into the fundamental physical mechanisms underlying the emergent morphology of the ER.

Abstract

The peripheral endoplasmic reticulum (ER) forms a dense, interconnected, and constantly evolving network of membrane-bound tubules in eukaryotic cells. While individual structural elements and the morphogens that stabilize them have been described, a quantitative understanding of the dynamic large-scale network topology remains elusive. We develop a physical model of the ER as an active liquid network, governed by a balance of tension-driven shrinking and new tubule growth. This minimalist model gives rise to steady-state network structures with density and rearrangement timescales predicted from the junction mobility and tubule spawning rate. Several parameter-independent geometric features of the liquid network model are shown to be representative of ER architecture in live mammalian cells. The liquid network model connects the timescales of distinct dynamic features such as ring closure and new tubule growth in the ER. Furthermore, it demonstrates how the steady-state network morphology on a cellular scale arises from the balance of microscopic dynamic rearrangements.

生物工学一般
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