文章基本信息

标题：DNA-relay mechanism is sufficient to explain ParA-dependent intracellular transport and patterning of single and multiple cargos
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作者：Ivan V. Surovtsev ; Manuel Campos ; Christine Jacobs-Wagner 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：46
页码：E7268-E7276
DOI：10.1073/pnas.1616118113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceAlthough intracellular patterning is crucial for cell function, the mechanisms by which spatial patterns arise often remain elusive. Here, we investigate the mechanism of intracellular patterning by the broadly conserved bacterial ParA/B systems, which drive the transport and partitioning of cellular cargos such as plasmids. We show that a simple model that considers only the known biochemical properties of the ParA and ParB proteins and the stochastic dynamics of chromosomal loci observed in vivo explains the spontaneous formation of propagating protein gradients, cargo oscillations, and equidistant patterns that are characteristic of ParA/B systems. Our study shows that stochastic processes and directionally random forces alone--without cytoskeletal elements or motor proteins--can result in directed motion and complex spatial patterning. Spatial ordering of macromolecular components inside cells is important for cellular physiology and replication. In bacteria, ParA/B systems are known to generate various intracellular patterns that underlie the transport and partitioning of low-copy-number cargos such as plasmids. ParA/B systems consist of ParA, an ATPase that dimerizes and binds DNA upon ATP binding, and ParB, a protein that binds the cargo and stimulates ParA ATPase activity. Inside cells, ParA is asymmetrically distributed, forming a propagating wave that is followed by the ParB-rich cargo. These correlated dynamics lead to cargo oscillation or equidistant spacing over the nucleoid depending on whether the cargo is in single or multiple copies. Currently, there is no model that explains how these different spatial patterns arise and relate to each other. Here, we test a simple DNA-relay model that has no imposed asymmetry and that only considers the ParA/ParB biochemistry and the known fluctuating and elastic dynamics of chromosomal loci. Stochastic simulations with experimentally derived parameters demonstrate that this model is sufficient to reproduce the signature patterns of ParA/B systems: the propagating ParA gradient correlated with the cargo dynamics, the single-cargo oscillatory motion, and the multicargo equidistant patterning. Stochasticity of ATP hydrolysis breaks the initial symmetry in ParA distribution, resulting in imbalance of elastic force acting on the cargo. Our results may apply beyond ParA/B systems as they reveal how a minimal system of two players, one binding to DNA and the other modulating this binding, can transform directionally random DNA fluctuations into directed motion and intracellular patterning.
关键词：intracellular patterning ; active transport ; ParA/B system ; partitioning ; mathematical model