A multi-adenylate cyclase regulator at the flagellar tip controls African trypanosome transmission.

A multi-adenylate cyclase regulator at the flagellar tip controls African trypanosome transmission.
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DOI:
10.1038/s41467-022-33108-z
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发表时间:
2022-09-16
影响因子:
16.6
通讯作者:
Boshart, Michael
Boshart, Michael
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Bachmaier, Sabine;Giacomelli, Giacomo;Calvo-Alvarez, Estefania;Vieira, Larissa Rezende;Van Den Abbeele, Jan;Aristodemou, Aris;Lorentzen, Esben;Gould, Matthew;Brennand, Ana;Dupuy, Jean-Wiliam;Forne, Ignasi;Imhof, Axel;Bramkamp, Marc;Salmon, Didier;Rotureau, Brice;Boshart, Michael

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来自纤毛微区的信号控制后生动物的发育过程。锥虫传播需要在采采蝇媒介消化道中发育和迁移。在体外,鞭毛 cAMP 信号传导与寄生虫社会运动 (SoMo) 相关,但揭示果蝇器官中定向迁移的控制具有挑战性。在这里,我们表明鞭毛尖端微域中腺苷酸环化酶(AC)复合物的组成对于采采蝇唾液腺(SG)定植和 SoMo 至关重要。环 AMP 反应蛋白 3 (CARP3) 结合并调节多种 AC 亚型。 CARP3 尖端定位取决于细胞骨架蛋白 FLAM8。 CARP3 重新定位远离尖端微域足以消除 SoMo 和果蝇 SG 定植。由于 carp3 和 flam8 敲除寄生虫的内在发育是正常的,AC 复合物介导的尖端信号传导专门控制寄生虫的迁移,从而控制传播。几种发育调节受体型AC亚型的参与可能表明所感知的体内信号的复杂性。锥虫可以感知信号分子并根据这些信号协调它们的运动,这种现象被称为社会运动(SoMo)。 Bachmaier 等人在此表明,环 AMP 反应蛋白 3 (CARP3) 定位于鞭毛尖端及其与多种不同腺苷酸环化酶的相互作用对于迁移到采采蝇唾液腺和 SoMo 至关重要,从而将 SoMo 和 cAMP 信号传导与锥虫传播联系起来。
Signaling from ciliary microdomains controls developmental processes in metazoans. Trypanosome transmission requires development and migration in the tsetse vector alimentary tract. Flagellar cAMP signaling has been linked to parasite social motility (SoMo) in vitro, yet uncovering control of directed migration in fly organs is challenging. Here we show that the composition of an adenylate cyclase (AC) complex in the flagellar tip microdomain is essential for tsetse salivary gland (SG) colonization and SoMo. Cyclic AMP response protein 3 (CARP3) binds and regulates multiple AC isoforms. CARP3 tip localization depends on the cytoskeletal protein FLAM8. Re-localization of CARP3 away from the tip microdomain is sufficient to abolish SoMo and fly SG colonization. Since intrinsic development is normal in carp3 and flam8 knock-out parasites, AC complex-mediated tip signaling specifically controls parasite migration and thereby transmission. Participation of several developmentally regulated receptor-type AC isoforms may indicate the complexity of the in vivo signals perceived. Trypanosomes can sense signal molecules and coordinate their movement in response to such signals, a phenomenon termed social motility (SoMo). Here, Bachmaier et al show that cyclic AMP response protein 3 (CARP3) localization to the flagellar tip and its interaction with a number of different adenylate cyclases is essential for migration to tsetse fly salivary glands and for SoMo, therewith linking SoMo and cAMP signaling to trypanosome transmission.
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