RRC ID 48859
Author Parsons LM, Grzeschik NA, Amaratunga K, Burke P, Quinn LM, Richardson HE.
Title A Kinome RNAi Screen in Drosophila Identifies Novel Genes Interacting with Lgl, aPKC, and Crb Cell Polarity Genes in Epithelial Tissues.
Journal G3 (Bethesda)
Abstract In both Drosophila melanogaster and mammalian systems, epithelial structure and underlying cell polarity are essential for proper tissue morphogenesis and organ growth. Cell polarity interfaces with multiple cellular processes that are regulated by the phosphorylation status of large protein networks. To gain insight into the molecular mechanisms that coordinate cell polarity with tissue growth, we screened a boutique collection of RNAi stocks targeting the kinome for their capacity to modify Drosophila "cell polarity" eye and wing phenotypes. Initially, we identified kinase or phosphatase genes whose depletion modified adult eye phenotypes associated with the manipulation of cell polarity complexes (via overexpression of Crb or aPKC). We next conducted a secondary screen to test whether these cell polarity modifiers altered tissue overgrowth associated with depletion of Lgl in the wing. These screens identified Hippo, Jun kinase (JNK), and Notch signaling pathways, previously linked to cell polarity regulation of tissue growth. Furthermore, novel pathways not previously connected to cell polarity regulation of tissue growth were identified, including Wingless (Wg/Wnt), Ras, and lipid/Phospho-inositol-3-kinase (PI3K) signaling pathways. Additionally, we demonstrated that the "nutrient sensing" kinases Salt Inducible Kinase 2 and 3 (SIK2 and 3) are potent modifiers of cell polarity phenotypes and regulators of tissue growth. Overall, our screen has revealed novel cell polarity-interacting kinases and phosphatases that affect tissue growth, providing a platform for investigating molecular mechanisms coordinating cell polarity and tissue growth during development.
Volume 7(8)
Pages 2497-2509
Published 2017-8-7
DOI 10.1534/g3.117.043513
PII g3.117.043513
PMID 28611255
PMC PMC5555457
MeSH Animals Cell Polarity / genetics* Drosophila Proteins / genetics* Drosophila Proteins / metabolism Drosophila melanogaster / genetics* Epistasis, Genetic* Epithelium / metabolism* Female Gene Ontology Genes, Insect* Genes, Modifier Genetic Testing* Male Membrane Proteins / genetics Membrane Proteins / metabolism Organ Size / genetics RNA Interference* Signal Transduction / genetics Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism Wings, Animal / anatomy & histology
IF 2.63
Times Cited 8
Drosophila 10522R-1 10532R-1 11438R-3 1388R-1 1495R-1 16973R-1 17299R-1 17520R-2 18255R-1 2055R-1 2309R-1 2615R-1 2615R-2 2905R-3 31640R-1 31643R-1 3632R-3 4549R-1 5092R-2 6238R-4 7393R-3 7643R-1 7693R-2 8565R-2 9156R-1 9578R-3 9578R-4 9856R-1