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

LI, A., YE, C., CHUANG J-Z., CÁCERES, A., AND SUNG, C-H.

DEVELOPMENTAL CELL

CELL PRESS

Lugar: United States; Año: 2013 vol. 26 p. 358 - 368

1534-5807

Primary cilia undergo cell-cycle-dependent assem- bly and disassembly. Emerging data suggest that ciliary resorption is a checkpoint for S phase reentry and that the activation of phospho(T94)Tctex-1 cou- ples 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 pro- gression by causing cilia to resorb. The mitogenic signals of IGF-1 are predominantly transduced through IGF-1 receptor (IGF-1R) on the cilia of fibro- blasts and epithelial cells. At the base of the cilium, phosphorylated IGF-1R activates an AGS3-regulated Gbg signaling pathway that subsequently recruits phospho(T94)Tctex-1 to the transition zone. Perturb- ing any component of this pathway in cortical progenitors induces premature neuronal differentia- tion at the expense of proliferation. These data suggest that during corticogenesis, a cilium-trans- duced, noncanonical IGF-1R-Gbg-phospho(T94) Tctex-1 signaling pathway promotes the proliferation of neural progenitors through modulation of ciliary resorption and G1 length.