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肌动蛋白网络动态稳态的定量调节。

Quantitative regulation of the dynamic steady state of actin networks.

机构信息

Courant Institute of Mathematical Sciences, New York University, New York, United States.

Department of Biology, New York University, New York, United States.

出版信息

Elife. 2019 Mar 14;8:e42413. doi: 10.7554/eLife.42413.

DOI:10.7554/eLife.42413
PMID:30869077
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6417862/
Abstract

Principles of regulation of actin network dimensions are fundamentally important for cell functions, yet remain unclear. Using both in vitro and in silico approaches, we studied the effect of key parameters, such as actin density, ADF/Cofilin concentration and network width on the network length. In the presence of ADF/Cofilin, networks reached equilibrium and became treadmilling. At the trailing edge, the network disintegrated into large fragments. A mathematical model predicts the network length as a function of width, actin and ADF/Cofilin concentrations. Local depletion of ADF/Cofilin by binding to actin is significant, leading to wider networks growing longer. A single rate of breaking network nodes, proportional to ADF/Cofilin density and inversely proportional to the square of the actin density, can account for the disassembly dynamics. Selective disassembly of heterogeneous networks by ADF/Cofilin controls steering during motility. Our results establish general principles on how the dynamic steady state of actin network emerges from biochemical and structural feedbacks.

摘要

肌动蛋白网络维度调节原理对细胞功能至关重要，但目前仍不清楚。我们采用体外和计算方法研究了关键参数（如肌动蛋白密度、ADF/Cofilin 浓度和网络宽度）对网络长度的影响。在 ADF/Cofilin 存在的情况下，网络达到平衡并开始进行踏车运动。在网络的尾部，网络会分解成大的片段。一个数学模型预测了网络长度作为宽度、肌动蛋白和 ADF/Cofilin 浓度的函数。ADF/Cofilin 通过与肌动蛋白结合而局部耗竭，导致更宽的网络生长更长。单个网络节点断裂的速率与 ADF/Cofilin 密度成正比，与肌动蛋白密度的平方成反比，可以解释解组装动力学。ADF/Cofilin 对异质网络的选择性解组装控制着运动过程中的转向。我们的研究结果确立了一般原理，即肌动蛋白网络的动态稳态如何从生化和结构反馈中产生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/97be9069539c/elife-42413-app1-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/de50418754e1/elife-42413-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/b75f43492bf2/elife-42413-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/4f1916a431ea/elife-42413-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/3314ad5b57eb/elife-42413-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/c7589d95892f/elife-42413-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/756a267d004f/elife-42413-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/03209a384cd2/elife-42413-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/a8579ed1fb81/elife-42413-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/da11da6b96bc/elife-42413-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/2d5347219054/elife-42413-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/43b8feadc5c5/elife-42413-app1-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/9c73d04899e0/elife-42413-app1-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/97be9069539c/elife-42413-app1-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/de50418754e1/elife-42413-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/b75f43492bf2/elife-42413-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/4f1916a431ea/elife-42413-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/3314ad5b57eb/elife-42413-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/c7589d95892f/elife-42413-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/756a267d004f/elife-42413-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/03209a384cd2/elife-42413-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/a8579ed1fb81/elife-42413-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/da11da6b96bc/elife-42413-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/2d5347219054/elife-42413-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/43b8feadc5c5/elife-42413-app1-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/9c73d04899e0/elife-42413-app1-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd76/6417862/97be9069539c/elife-42413-app1-fig3.jpg

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