细胞中发动蛋白寡聚化的调控：发动蛋白与肌动蛋白相互作用及其GTP酶活性的作用
Regulation of dynamin oligomerization in cells: the role of dynamin-actin interactions and its GTPase activity.
作者信息
Gu Changkyu, Chang Joann, Shchedrina Valentina A, Pham Vincent A, Hartwig John H, Suphamungmee Worawit, Lehman William, Hyman Bradley T, Bacskai Brian J, Sever Sanja
机构信息
Division of Nephrology, Massachusetts General Hospital, Charlestown, MA, 02129, USA.
出版信息
Traffic. 2014 Aug;15(8):819-38. doi: 10.1111/tra.12178. Epub 2014 Jun 24.
Abstract
Dynamin is a 96-kDa protein that has multiple oligomerization states that influence its GTPase activity. A number of different dynamin effectors, including lipids, actin filaments, and SH3-domain-containing proteins, have been implicated in the regulation of dynamin oligomerization, though their roles in influencing dynamin oligomerization have been studied predominantly in vitro using recombinant proteins. Here, we identify higher order dynamin oligomers such as rings and helices in vitro and in live cells using fluorescence lifetime imaging microscopy (FLIM). FLIM detected GTP- and actin-dependent dynamin oligomerization at distinct cellular sites, including the cell membrane and transition zones where cortical actin transitions into stress fibers. Our study identifies a major role for direct dynamin-actin interactions and dynamin's GTPase activity in the regulation of dynamin oligomerization in cells.
摘要
发动蛋白是一种96千道尔顿的蛋白质，具有多种寡聚化状态，这些状态会影响其GTP酶活性。许多不同的发动蛋白效应物，包括脂质、肌动蛋白丝和含SH3结构域的蛋白质，都与发动蛋白寡聚化的调节有关，尽管它们在影响发动蛋白寡聚化方面的作用主要是在体外使用重组蛋白进行研究的。在这里，我们使用荧光寿命成像显微镜（FLIM）在体外和活细胞中鉴定出更高阶的发动蛋白寡聚体，如环和螺旋。FLIM在不同的细胞位点检测到了依赖于GTP和肌动蛋白的发动蛋白寡聚化，包括细胞膜和皮质肌动蛋白转变为应力纤维的过渡区。我们的研究确定了直接的发动蛋白-肌动蛋白相互作用和发动蛋白的GTP酶活性在细胞中发动蛋白寡聚化调节中的主要作用。
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本文引用的文献
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Dynamin2 organizes lamellipodial actin networks to orchestrate lamellar actomyosin.发动蛋白2组织片状伪足肌动蛋白网络以协调片状肌动球蛋白。
PLoS One. 2014 Apr 7;9(4):e94330. doi: 10.1371/journal.pone.0094330. eCollection 2014.
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Dynamin rings: not just for fission.动力蛋白环：不仅仅用于分裂。
Traffic. 2013 Dec;14(12):1194-9. doi: 10.1111/tra.12116. Epub 2013 Sep 19.
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Role of dynamin, synaptojanin, and endophilin in podocyte foot processes.动力蛋白、突触结合蛋白和内收蛋白在足细胞足突中的作用。
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Crystal structure of nucleotide-free dynamin.无核苷酸状态下的动力蛋白的晶体结构。
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Direct dynamin-actin interactions regulate the actin cytoskeleton.直接的动力蛋白-肌动蛋白相互作用调节肌动蛋白细胞骨架。
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