在线粒体裂变中由ER相关的FORMININF2介导的一步,依赖于ACTIN
Farida Korobova1, Vinay Ramabhadran, Henry N Higgs
1Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
概括
在内质网膜中由反转的formin 2 (INF2) 驱动的阿克丁聚合,对于线粒体裂变至关重要. 这一过程先于动相关蛋白1 (Drp1) 的作用,为查尔科-玛丽-图斯病提供了洞察力.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 线粒体分裂对于细胞功能至关重要.
- 与胺相关的蛋白1 (Drp1) 中介于线粒体裂变.
- 细胞内膜网膜 (ER) 和线粒体相互作用增强了裂变,但DRp1的招募机制仍然不清楚.
研究的目的:
- 为了阐明Drp1在裂变过程中招募到线粒体的机制.
- 为了研究actin在线粒体裂变中的作用.
- 探索INF2,actin和线粒体动力学之间的联系.
主要方法:
- 哺乳动物细胞培养.
- 免疫光显微镜可用于可视化线粒体,ER,actin和INF2.
- 基因操纵以研究INF2功能和actin聚合.
- 生物化学测试用于评估蛋白质相互作用和细胞过程.
主要成果:
- 为了高效的线粒体裂变,需要由ER局部倒置formin 2 (INF2) 促进的动氨酸聚合.
- 在裂变通路中,INF2在Drp1的上游作用.
- 动氨酸丝在ER-线粒体接触点积聚,调解初始收缩.
- 由INF2诱导的丝纤维促进了DRp1依赖的二次收缩.
结论:
- 通过INF2介导的乙聚合是线粒体裂变的关键上游调节器.
- 这种机制为查科-玛丽-病中观察到的细胞缺陷提供了潜在的解释,这种缺陷与INF2突变有关.
相关概念视频
Generation of Straight or Branched Actin Filaments
The straight or branched structure formation of actin filaments is controlled by nucleating proteins such as the formins and Arp2/3 complex. Formin-mediated assembly results in straight filaments, whereas Arp2/3 protein complex-mediated assembly results in branched actin filaments.
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
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Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
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Actin Filament Depolymerization
Actin filaments (F-actin) are composed of actin subunits. The dissociation of actin monomers can occur from either end of F-actin. The rate of dissociation is faster from the minus-end or the pointed end, where the actin subunits exist with a bound ADP, together known as ADP-actin. The depolymerization of F-actin is aided by proteins, including the actin-depolymerizing factor (ADF) and cofilin family of proteins, gelsolin, and glia maturation factor (GMF).
In F-actin, the ADF/cofilin proteins...
In F-actin, the ADF/cofilin proteins...
Disassembly of Intermediate Filaments
Intermediate filaments (IFs) do not undergo spontaneous disassembly. Enzymes, kinases, and phosphatases add and remove phosphates from specific sites to regulate their disassembly. The IF concentration in the cytoplasm also regulates the disassembly. If the concentration crosses a threshold, it activates the protein kinases in the vicinity, allowing the phosphorylation of IFs.
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
Actin Polymerization
Actin polymerization occurs through the head-to-tail association of binding sites on monomeric actin or G-actin to form filamentous or F-actin. The polymerization can be divided into three phases ̶ nucleation, elongation, and steady-state phase.
The nucleation phase involves forming a stable nucleus consisting of three actin monomers to form a new actin filament. Actin-binding proteins such as formins and Arp2/3 complex help filament growth post-nucleation. The Formins form straight actin...
The nucleation phase involves forming a stable nucleus consisting of three actin monomers to form a new actin filament. Actin-binding proteins such as formins and Arp2/3 complex help filament growth post-nucleation. The Formins form straight actin...
The Contractile Ring
Contractile rings are composed of microfilaments and are responsible for separating the daughter cells during cytokinesis. Contractile ring assembly proceeds along with other cell cycle events; however, very few mechanistic details are known about the timing and coordination of the contractile rings with the cell cycle.
A small GTPase, RhoA, controls the function and assembly of the contractile ring. RhoA belongs to the Ras superfamily of proteins. The activation of formins by RhoA promotes...
A small GTPase, RhoA, controls the function and assembly of the contractile ring. RhoA belongs to the Ras superfamily of proteins. The activation of formins by RhoA promotes...


