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首页> 外文期刊>Developmental cell >The PI3K Class III Complex Promotes Axon Pruning by Downregulating a Ptc-Derived Signal via Endosome-Lysosomal Degradation.
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The PI3K Class III Complex Promotes Axon Pruning by Downregulating a Ptc-Derived Signal via Endosome-Lysosomal Degradation.

机译：PI3K III类复合物通过内体-溶酶体降解下调Ptc衍生信号来促进轴突修剪。

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摘要

Developmental axon pruning is essential for wiring the mature nervous system, but its regulation remains poorly understood. Here we show that the endosomal-lysosomal pathway regulates developmental pruning of Drosophila mushroom body γ neurons. We demonstrate that the UV radiation resistance-associated gene (UVRAG) functions together with all core components of the phosphatidylinositol 3-kinase class III (PI3K-cIII) complex to promote pruning via the endocytic pathway. By studying several PI(3)P binding proteins, we found that Hrs, a subunit of the ESCRT-0 complex, required for multivesicular body (MVB) maturation, is essential for normal pruning progression. Thus, we hypothesized the existence of an inhibitory signal that needs to be downregulated. Finally, our data suggest that the Hedgehog receptor, Patched, is the source of this inhibitory signal likely functioning in a Smo-independent manner. Taken together, our in?vivo study demonstrates that the PI3K-cIII complex is essential for downregulating Patched via the endosomal-lysosomal pathway to execute axon pruning.
机译：发育中的轴突修剪对于连接成熟的神经系统至关重要，但对其调节的了解仍然很少。在这里，我们显示内体-溶酶体途径调节果蝇蘑菇体γ神经元的发育修剪。我们证明了抗紫外线辐射相关基因（UVRAG）与磷脂酰肌醇3-激酶III类（PI3K-cIII）复杂的所有核心成分一起促进通过内吞途径进行修剪。通过研究几种PI（3）P结合蛋白，我们发现Hrs，ESCRT-0复杂的一个亚基，多泡体（MVB）成熟所需，对于正常的修剪进程至关重要。因此，我们假设需要抑制信号的存在。最后，我们的数据表明，Hedgehog受体Patched是这种抑制信号的来源，可能以Smo独立的方式起作用。综上所述，我们的体内研究表明，PI3K-cIII复合物对于通过内体-溶酶体途径下调执行轴突修剪的修补程序至关重要。

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