Juvenile hormone(JH) and 20-hydroxyecdysone(20 E) coordinately regulate development and metamorphosis in insects. Two JH intracellular receptors, methoprene-tolerant(Met) and germ-cell expressed(Gce), have been identi...Juvenile hormone(JH) and 20-hydroxyecdysone(20 E) coordinately regulate development and metamorphosis in insects. Two JH intracellular receptors, methoprene-tolerant(Met) and germ-cell expressed(Gce), have been identified in the fruit fly Drosophila melanogaster. To investigate JH membrane signaling pathway without the interference from JH intracellular signaling, we characterized phosphoproteome profiles of the Met gce double mutant in the absence or presence of JH in both chronic and acute phases.Functioning through a potential receptor tyrosine kinase and phospholipase C pathway, JH membrane signaling activated protein kinase C(PKC) which phosphorylated ultraspiracle(USP) at Ser35, the PKC phosphorylation site required for the maximal action of 20 E through its nuclear receptor complex Ec RUSP. The usp;mutant, in which Ser was replaced with Ala at position 35 by genome editing, showed decreased expression of Halloween genes that are responsible for ecdysone biosynthesis and thus attenuated 20 E signaling that delayed developmental timing. The usp;mutant also showed lower Yorkie activity that reduced body size. Altogether, JH membrane signaling phosphorylates USP at Ser35 and thus potentiates 20 E action that regulates the normal fly development. This study helps better understand the complex JH signaling network.展开更多
The Hippo pathway plays a crucial role in controlling organ size by inhibiting cell proliferation and promoting cell death.Recent findings implicate that this pathway is involved in the process of intestinal regenerat...The Hippo pathway plays a crucial role in controlling organ size by inhibiting cell proliferation and promoting cell death.Recent findings implicate that this pathway is involved in the process of intestinal regeneration and tumorigenesis.Here we summarize current studies for the function of the Hippo signaling pathway in intestinal homeostasis,regeneration and tumorigenesis,and the crosstalk between the Hippo signaling pathway and other major signaling pathways,i.e.Wnt,Notch and Jak/Stat signaling pathways in intestinal compartment.展开更多
The evolutionarily conserved Hippo signaling pathway plays an important role in organ size control by regulating cell proliferation and apoptosis.Here,we identify Lingerer(Lig)as a growth suppressor using RNAi modifyi...The evolutionarily conserved Hippo signaling pathway plays an important role in organ size control by regulating cell proliferation and apoptosis.Here,we identify Lingerer(Lig)as a growth suppressor using RNAi modifying screen in Drosophila melanogaster.Loss of lig increases organ size and upregulates bantam(ban)and the expression of the Hippo pathway target genes,while overexpression of lig results in diminished ban expression and organ size reduction.We demonstrate that Lig C-terminal exhibits dominant-negative function on growth and ban expression,and thus plays an important role in organ size control and ban regulation.In addition,we provide evidence that both Yki and Mad are essential for Lig-induced ban expression.We also show that Lig regulates the expression of the Hippo pathway target genes partially via Yorkie.Moreover,we find that Lig physically interacts with and requires Salvador to restrict cell growth.Taken together,we demonstrate that Lig functions as a critical growth suppressor to control organ size via ban and Hippo signaling.展开更多
基金supported by the National Natural Science Foundation of China(31620103917 31970459 32070441 31702054 and 31930014)the Shenzhen Science and Technology Program(20180411143628272)the Natural Science Foundation of Guangdong Province(2019A1515011899)。
文摘Juvenile hormone(JH) and 20-hydroxyecdysone(20 E) coordinately regulate development and metamorphosis in insects. Two JH intracellular receptors, methoprene-tolerant(Met) and germ-cell expressed(Gce), have been identified in the fruit fly Drosophila melanogaster. To investigate JH membrane signaling pathway without the interference from JH intracellular signaling, we characterized phosphoproteome profiles of the Met gce double mutant in the absence or presence of JH in both chronic and acute phases.Functioning through a potential receptor tyrosine kinase and phospholipase C pathway, JH membrane signaling activated protein kinase C(PKC) which phosphorylated ultraspiracle(USP) at Ser35, the PKC phosphorylation site required for the maximal action of 20 E through its nuclear receptor complex Ec RUSP. The usp;mutant, in which Ser was replaced with Ala at position 35 by genome editing, showed decreased expression of Halloween genes that are responsible for ecdysone biosynthesis and thus attenuated 20 E signaling that delayed developmental timing. The usp;mutant also showed lower Yorkie activity that reduced body size. Altogether, JH membrane signaling phosphorylates USP at Ser35 and thus potentiates 20 E action that regulates the normal fly development. This study helps better understand the complex JH signaling network.
基金supported by grants from the China’s 1000 Young Talents Program,the 111 Project of The Ministration of Education of China(No.B06016)the Fundamental Research Funds for the Central Universities of China(No.2010111079)+1 种基金National Natural Science Foundation of China(Grant No.81101503)and Natural Science Foundation of Fujian(No.2011J05096)supported by the RO1 awards CA136567(JA),DK17776(JA)and institutional funds.The authors have no financial conflicts to disclose.
文摘The Hippo pathway plays a crucial role in controlling organ size by inhibiting cell proliferation and promoting cell death.Recent findings implicate that this pathway is involved in the process of intestinal regeneration and tumorigenesis.Here we summarize current studies for the function of the Hippo signaling pathway in intestinal homeostasis,regeneration and tumorigenesis,and the crosstalk between the Hippo signaling pathway and other major signaling pathways,i.e.Wnt,Notch and Jak/Stat signaling pathways in intestinal compartment.
基金This work is supported by grants from the National Basic Research Program of China(973 Program)(2010CB912101,2012CB945001,2011CB943902)the‘Strategic Priority Research Program’of the Chinese Academy of Sciences(XDA01010406)National Natural Science Foundation of China(31171394,31371462).
文摘The evolutionarily conserved Hippo signaling pathway plays an important role in organ size control by regulating cell proliferation and apoptosis.Here,we identify Lingerer(Lig)as a growth suppressor using RNAi modifying screen in Drosophila melanogaster.Loss of lig increases organ size and upregulates bantam(ban)and the expression of the Hippo pathway target genes,while overexpression of lig results in diminished ban expression and organ size reduction.We demonstrate that Lig C-terminal exhibits dominant-negative function on growth and ban expression,and thus plays an important role in organ size control and ban regulation.In addition,we provide evidence that both Yki and Mad are essential for Lig-induced ban expression.We also show that Lig regulates the expression of the Hippo pathway target genes partially via Yorkie.Moreover,we find that Lig physically interacts with and requires Salvador to restrict cell growth.Taken together,we demonstrate that Lig functions as a critical growth suppressor to control organ size via ban and Hippo signaling.
