Journal
EMBO JOURNAL
Volume 33, Issue 19, Pages 2247-2260Publisher
WILEY
DOI: 10.15252/embj.201488466
Keywords
colorectal cancer; microtubule glycylation; primary cilia; proliferation; tubulin posttranslational modification
Categories
Funding
- Institut Curie
- CNRS
- INSERM
- Fondation Pierre-Gilles de Gennes 3T-grant
- FRM grant [DEQ20081213977, FDT20120925331]
- ANR [08-JCJC-0007, ANR-12-BSV20007, ANR-10-LBX-0038]
- IDEX Idex PSL [ANR-10-IDEX-0001-02 PSL]
- INCA grant [2009-1-PL BIO-12-IC-1]
- ARC programme labellise [SL220120605303]
- EMBO short-term fellowship [ASTF 452014]
- EMBO YIP
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TTLL3 and TTLL8 are tubulin glycine ligases catalyzing posttranslational glycylation of microtubules. We show here for the first time that these enzymes are required for robust formation of primary cilia. We further discover the existence of primary cilia in colon and demonstrate that TTLL3 is the only glycylase in this organ. As a consequence, colon epithelium shows a reduced number of primary cilia accompanied by an increased rate of cell division in TTLL3-knockout mice. Strikingly, higher proliferation is compensated by faster tissue turnover in normal colon. In a mouse model for tumorigenesis, lack of TTLL3 strongly promotes tumor development. We further demonstrate that decreased levels of TTLL3 expression are linked to the development of human colorectal carcinomas. Thus, we have uncovered a novel role for tubulin glycylation in primary cilia maintenance, which controls cell proliferation of colon epithelial cells and plays an essential role in colon cancer development.
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