National Centre for Biological Sciences-TIFR, GKVK Campus, Bellary Road, Bangalore, 560065, India.
National Centre for Biological Sciences-TIFR, GKVK Campus, Bellary Road, Bangalore, 560065, India
G3 (Bethesda). 2020 Jan 7;10(1):57-67. doi: 10.1534/g3.119.400851.
Phosphoinositides are lipid signaling molecules that regulate several conserved sub-cellular processes in eukaryotes, including cell growth. Phosphoinositides are generated by the enzymatic activity of highly specific lipid kinases and phosphatases. For example, the lipid PIP, the Class I PI3 kinase that generates it and the phosphatase PTEN that metabolizes it are all established regulators of growth control in metazoans. To identify additional functions for phosphoinositides in growth control, we performed a genetic screen to identify proteins which when depleted result in altered tissue growth. By using RNA-interference mediated depletion coupled with mosaic analysis in developing eyes, we identified and classified additional candidates in the developing eye that regulate growth either cell autonomously or via cell-cell interactions. We report three genes: , and that are important for growth regulation and suggest that these are likely to act via cell-cell interactions in the developing eye. Our findings define new avenues for the understanding of growth regulation in metazoan tissue development by phosphoinositide metabolizing proteins.
磷酸肌醇是一类脂质信号分子，在真核生物中调节着多种保守的亚细胞过程，包括细胞生长。磷酸肌醇是由高度特异的脂质激酶和磷酸酶的酶活性产生的。例如，脂质 PIP、产生它的 I 类 PI3 激酶和代谢它的磷酸酶 PTEN 都是后生动物生长控制的既定调节剂。为了确定磷酸肌醇在生长控制中的其他功能，我们进行了遗传筛选，以鉴定那些耗尽后会导致组织生长改变的蛋白质。通过使用 RNA 干扰介导的耗竭，结合在发育中的眼睛中的嵌合体分析，我们在发育中的眼睛中鉴定并分类了另外一些候选基因，它们通过细胞自主或细胞间相互作用来调节生长。我们报告了三个基因： 、 和 ，它们对生长调控很重要，并且表明这些基因可能通过细胞间相互作用在发育中的眼睛中发挥作用。我们的发现通过磷酸肌醇代谢蛋白为后生动物组织发育中的生长调控提供了新的途径。
