Growth factor-independent mTORC1 signaling promotes primary cilia length via suppression of autophagy

Jong Shin; Khaled Tighanimine; Yann Cormerais; Dean M Rosenthal; Pratima Niroula; Samuel C Lapp; Krystle C Kalafut; Madi Y Cisse; Sandra Schrötter; Brendan D Manning

doi:10.1016/j.isci.2025.114204

Growth factor-independent mTORC1 signaling promotes primary cilia length via suppression of autophagy

iScience. 2025 Nov 25;28(12):114204. doi: 10.1016/j.isci.2025.114204. eCollection 2025 Dec 19.

Authors

Jong Shin^{1

2}, Khaled Tighanimine^{1

2}, Yann Cormerais^{1

2}, Dean M Rosenthal^{1

2}, Pratima Niroula^{1

2}, Samuel C Lapp^{1

2}, Krystle C Kalafut^{1

2}, Madi Y Cisse^{1

2}, Sandra Schrötter^{1

2}, Brendan D Manning^{1

2}

Affiliations

¹ Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
² Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

Abstract

The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1), a sensor of growth signals that control cell growth, has been studied mainly in proliferating cells. Primary cilia are sensory organelles present on most quiescent cells and are essential for receiving environmental and developmental signals. Given that ciliated cells are non-proliferative, we investigated whether mTORC1 signaling influences primary cilia growth. Here, we show that mTORC1 promotes cilia elongation without affecting ciliogenesis by suppressing autophagy. Inhibiting mTORC1 through pharmacological, nutritional, or genetic interventions shortened primary cilia, whereas activation of the pathway elongated them. Furthermore, pharmacological or genetic inhibition of autophagy-a key downstream process blocked by mTORC1-elongated primary cilia and rendered them resistant to mTORC1 inhibition. These mTORC1-mediated effects extend to mouse neurons ex vivo and in vivo. Thus, the mTORC1-mediated regulation of autophagy controls primary cilia length and may contribute to diseases in which ciliary function is altered, referred to as ciliopathies.

Keywords: Cell biology; Molecular physiology.

Abstract

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