TRiC/CCT chaperonins are essential for organ growth by interacting with insulin/TOR signaling in Drosophila

Oncogene
Ah-Ram Kim, Kwang-Wook Choi

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.

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Citations

Nov 14, 2019·Cellular and Molecular Bioengineering·Aya M SalehSarah Calve
Mar 3, 2021·Proceedings of the National Academy of Sciences of the United States of America·Hong-Wen TangNorbert Perrimon
Oct 19, 2021·Frontiers in Cell and Developmental Biology·Najma ShaheenMuhammad Tariq

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Methods Mentioned

BETA
co-immunoprecipitation
KAIST
pulldown
PCR
transfection
immunoprecipitation

Software Mentioned

GenetiVision

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