Concerted action of two formins in gliding motility and host cell invasion by Toxoplasma gondii.
Concerted action of two formins in gliding motility and host cell invasion by Toxoplasma gondii.
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DOI：
10.1371/journal.ppat.1001132
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发表时间：
2010-10-07
期刊：
影响因子：
6.7
通讯作者：
Soldati-Favre D
中科院分区：
文献类型：
--
作者：
Daher W;Plattner F;Carlier MF;Soldati-Favre D
The invasive forms of apicomplexan parasites share a conserved form of gliding motility that powers parasite migration across biological barriers, host cell invasion and egress from infected cells. Previous studies have established that the duration and direction of gliding motility are determined by actin polymerization; however, regulators of actin dynamics in apicomplexans remain poorly characterized. In the absence of a complete ARP2/3 complex, the formin homology 2 domain containing proteins and the accessory protein profilin are presumed to orchestrate actin polymerization during host cell invasion. Here, we have undertaken the biochemical and functional characterization of two Toxoplasma gondii formins and established that they act in concert as actin nucleators during invasion. The importance of TgFRM1 for parasite motility has been assessed by conditional gene disruption. The contribution of each formin individually and jointly was revealed by an approach based upon the expression of dominant mutants with modified FH2 domains impaired in actin binding but still able to dimerize with their respective endogenous formin. These mutated FH2 domains were fused to the ligand-controlled destabilization domain (DD-FKBP) to achieve conditional expression. This strategy proved unique in identifying the non-redundant and critical roles of both formins in invasion. These findings provide new insights into how controlled actin polymerization drives the directional movement required for productive penetration of parasites into host cells. Gliding motility is a unique property of the Apicomplexa. Members of this phylum include important human and animal pathogens. An actomyosin-based machine powers parasite motility and is crucial for parasite migration across biological barriers, host cell invasion and egress from infected cells. The timing, duration and orientation of the gliding motility are tightly regulated to insure successful establishment of infection. Controlled polymerization of actin filaments is a key feature of motility, and we demonstrate here the implication of two formins that catalyse actin nucleation and fast assembly of filaments. Both proteins are essential and act in concert during productive penetration of the parasite into host cells.
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影响因子：
9.8
作者：
Bozdech, Zbynek;Llinas, Manuel;Pulliam, Brian Lee;Wong, Edith D;Zhu, Jingchun;DeRisi, Joseph L
通讯作者：
DeRisi, Joseph L
影响因子：
3.3
作者：
Håkansson, S;Morisaki, H;Sibley, LD
通讯作者：
Sibley, LD
影响因子：
11.4
作者：
Helfer, E;Nevalainen, EM;Carlier, MF
通讯作者：
Carlier, MF
比较基因组分析揭示了Apicomplexan寄生虫中保守的肌动蛋白样蛋白家族。
影响因子：
4.4
作者：
Gordon JL;Sibley LD
通讯作者：
Sibley LD
影响因子：
48
作者：
Herm-Goetz, Angelika;Agop-Nersesian, Carolina;Meissner, Markus
通讯作者：
Meissner, Markus