Heterotrimeric G proteins regulate a noncanonical function of septate junction proteins to maintain cardiac integrity in Drosophila.

Heterotrimeric G proteins regulate a noncanonical function of septate junction proteins to maintain cardiac integrity in Drosophila.
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DOI:
10.1016/j.devcel.2008.10.001
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发表时间:
2008-11
期刊:
影响因子:
11.8
通讯作者:
Olson, Eric N.
Olson, Eric N.
中科院分区:
生物学1区
文献类型:
--
作者:
Yi, Peng;Johnson, Aaron N.;Han, Zhe;Wu, Jiang;Olson, Eric N.

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调控心脏形态和心脏完整性的基因网络在很大程度上是未知的。我们之前报道了异三聚体G蛋白γ亚基1 (Gγ1)在果蝇心脏-心包细胞粘附中的作用。我们发现G-oα47A和g - β 13f与g - γ1协同维持心脏的完整性。心脏-心包细胞粘附也依赖于间隔连接(SJ)蛋白Neurexin-IV (Nrx-IV)、sinous、Coracle和Nervana2,这些蛋白与g γ - 1在一个共同的途径中起作用。此外,g γ - 1信号是SJ蛋白正确定位所必需的,至少一种SJ蛋白Nrx-IV的缺失会导致心腔塌陷。这些结果令人惊讶,因为胚胎心脏缺乏SJ,这表明SJ蛋白在果蝇中发挥非规范功能来维持心脏的完整性。我们的发现揭示了一个以前未被认识的基因网络的组成部分,该网络将g蛋白信号与心脏的新结构成分结合起来。
The gene networks regulating heart morphology and cardiac integrity are largely unknown. We previously reported a role for the heterotrimeric G protein γ subunit 1 (Gγ1) in mediating cardial-pericardial cell adhesion in Drosophila. Here we show G-oα47A and Gβ13F cooperate with Gγ1 to maintain cardiac integrity. Cardial-pericardial cell adhesion also relies on the septate junction (SJ) proteins Neurexin-IV (Nrx-IV), Sinuous, Coracle, and Nervana2, and which together function in a common pathway with Gγ1. Furthermore, Gγ1 signaling is required for proper SJ protein localization, and loss of at least one SJ protein, Nrx-IV, induces cardiac lumen collapse. These results are surprising because the embryonic heart lacks SJs and suggest that SJ proteins perform non-canonical functions to maintain cardiac integrity in Drosophila. Our findings unveil the components of a previously unrecognized network of genes that couple G-protein signaling with novel structural constituents of the heart.
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