关键词: MST2 PP2A-A (PP2A-29B) PP2A-C (Mts) STRIATIN TAZ YAP

Mesh : Adaptor Proteins, Signal Transducing Animals Drosophila / metabolism Drosophila Proteins / genetics metabolism Drosophila melanogaster / genetics metabolism Epithelium / metabolism Protein Phosphatase 2 / genetics metabolism Protein Serine-Threonine Kinases / genetics metabolism Retina / metabolism

来  源:   DOI:10.1242/jcs.237834   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
The specification of organs, tissues and cell types results from cell fate restrictions enacted by nuclear transcription factors under the control of conserved signaling pathways. The progenitor epithelium of the Drosophila compound eye, the eye imaginal disc, is a premier model for the study of such processes. Early in development, apposing cells of the eye disc are established as either retinal progenitors or support cells of the peripodial epithelium (PE), in a process whose genetic and mechanistic determinants are poorly understood. We have identified protein phosphatase 2A (PP2A), and specifically a STRIPAK-PP2A complex that includes the scaffolding and substrate-specificity components Cka, Strip and SLMAP, as a critical player in the retina-PE fate choice. We show that these factors suppress ectopic retina formation in the presumptive PE and do so via the Hippo signaling axis. STRIPAK-PP2A negatively regulates Hippo kinase, and consequently its substrate Warts, to release the transcriptional co-activator Yorkie into the nucleus. Thus, a modular higher-order PP2A complex refines the activity of this general phosphatase to act in a precise specification of cell fate.
摘要:
器官的规格,组织和细胞类型是由保守信号通路控制下的核转录因子限制细胞命运的结果。果蝇复眼的祖先上皮,眼睛想象盘,是研究此类过程的首要模型。在发展初期,视盘的细胞被建立为视网膜祖细胞或周围上皮(PE)的支持细胞,在一个遗传和机械决定因素知之甚少的过程中。我们已经鉴定了蛋白磷酸酶2A(PP2A),特别是STRIPAK-PP2A复合物,包括支架和底物特异性成分Cka,Strip和SLMAP,作为视网膜-PE命运选择的关键参与者。我们表明,这些因素在假定的PE中抑制异位视网膜形成,并通过Hippo信号轴进行。STRIPAK-PP2A负调节Hippo激酶,因此它的基底疣,将转录共激活因子Yorkie释放到细胞核中。因此,模块化的高阶PP2A复合物完善了这种一般磷酸酶的活性,以精确地说明细胞命运。
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