RRC ID 54466
Author Kim AR, Choi KW.
Title TRiC/CCT chaperonins are essential for organ growth by interacting with insulin/TOR signaling in Drosophila.
Journal Oncogene
Abstract Organ size is regulated by intercellular signaling for cell growth and proliferation. The TOR pathway mediates a key signaling mechanism for controlling cell size and number in organ growth. Chaperonin containing TCP-1 (CCT) is a complex that assists protein folding and function, but its role in animal development is largely unknown. Here we show that the CCT complex is required for organ growth by interacting with the TOR pathway in Drosophila. Reduction of CCT4 results in growth defects by affecting both cell size and proliferation. Loss of CCT4 causes preferential cell death anterior to the morphogenetic furrow in the eye disc and within wing pouch in the wing disc. Depletion of any CCT subunit in the eye disc results in headless phenotype. Overgrowth by active TOR signaling is suppressed by CCT RNAi. The CCT complex physically interacts with TOR signaling components including TOR, Rheb, and S6K. Loss of CCT leads to decreased phosphorylation of S6K and S6 while increasing phosphorylation of Akt. Insulin/TOR signaling is also necessary and sufficient for promoting CCT complex transcription. Our data provide evidence that the CCT complex regulates organ growth by directly interacting with the TOR signaling pathway.
Volume 38(24)
Pages 4739-4754
Published 2019-6-1
DOI 10.1038/s41388-019-0754-1
PII 10.1038/s41388-019-0754-1
PMID 30792539
PMC PMC6756063
MeSH Animal Structures / growth & development* Animal Structures / metabolism Animals Animals, Genetically Modified Chaperonin Containing TCP-1 / physiology* Chaperonins / genetics Chaperonins / physiology* Drosophila / embryology Drosophila / genetics Drosophila / growth & development Drosophila / metabolism Drosophila Proteins / genetics Drosophila Proteins / metabolism Gene Expression Regulation, Developmental Insulin / metabolism* Multiprotein Complexes / physiology Organogenesis / genetics Signal Transduction / genetics TOR Serine-Threonine Kinases / metabolism* Wings, Animal / growth & development Wings, Animal / metabolism
IF 6.634
Times Cited 3
Drosophila 5374R-2 7033R-1 8977R-1 5525R-3 8439R-1 8351R-3 8258R-2 DGRC#111690 DGRC#141081