IGF-1 activates a cilium-localized noncanonical Gβγ signaling pathway that regulates cell-cycle progression.

TitleIGF-1 activates a cilium-localized noncanonical Gβγ signaling pathway that regulates cell-cycle progression.
Publication TypeJournal Article
Year of Publication2013
AuthorsYeh C, Li A, Chuang J-Z, Saito M, Cáceres A, Sung C-H
JournalDev Cell
Volume26
Issue4
Pagination358-68
Date Published2013 Aug 26
ISSN1878-1551
KeywordsAnimals, Cell Cycle, Cell Proliferation, Cilia, Dyneins, GTP-Binding Protein beta Subunits, GTP-Binding Protein gamma Subunits, Humans, Insulin-Like Growth Factor I, Mice, Mitogens, Models, Biological, Neocortex, Phosphorylation, Receptor, IGF Type 1, S Phase, Signal Transduction, Stem Cells
Abstract

Primary cilia undergo cell-cycle-dependent assembly and disassembly. Emerging data suggest that ciliary resorption is a checkpoint for S phase reentry and that the activation of phospho(T94)Tctex-1 couples these two events. However, the environmental cues and molecular mechanisms that trigger these processes remain unknown. Here, we show that insulin-like growth-1 (IGF-1) accelerates G1-S progression by causing cilia to resorb. The mitogenic signals of IGF-1 are predominantly transduced through IGF-1 receptor (IGF-1R) on the cilia of fibroblasts and epithelial cells. At the base of the cilium, phosphorylated IGF-1R activates an AGS3-regulated Gβγ signaling pathway that subsequently recruits phospho(T94)Tctex-1 to the transition zone. Perturbing any component of this pathway in cortical progenitors induces premature neuronal differentiation at the expense of proliferation. These data suggest that during corticogenesis, a cilium-transduced, noncanonical IGF-1R-Gβγ-phospho(T94)Tctex-1 signaling pathway promotes the proliferation of neural progenitors through modulation of ciliary resorption and G1 length.

DOI10.1016/j.devcel.2013.07.014
Alternate JournalDev. Cell
PubMed ID23954591
PubMed Central IDPMC3790638
Grant ListR01 EY011307 / EY / NEI NIH HHS / United States
R01 EY016805 / EY / NEI NIH HHS / United States
EY016805 / EY / NEI NIH HHS / United States
EY11307 / EY / NEI NIH HHS / United States