LRIG1 controls proliferation of adult neural stem cells by facilitating TGFβ and BMP signalling pathways.

Autor: Ouzikov, Stephanie, Edwards, Kyshona M., Anandampillai, Tanvi, Watanabe, Samuel, Lozano Casasbuenas, Daniela, Siu, Karen K., Harkins, Danyon, Dou, Aaron, Jeong, Danielle, Lee, Jeffrey E., Yuzwa, Scott A.
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Zdroj: Communications Biology; 7/10/2024, Vol. 7 Issue 1, p1-13, 13p
Abstrakt: Adult Neural Stem Cells (aNSCs) in the ventricular-subventricular zone (V-SVZ) are largely quiescent. Here, we characterize the mechanism underlying the functional role of a cell-signalling inhibitory protein, LRIG1, in the control of aNSCs proliferation. Using Lrig1 knockout models, we show that Lrig1 ablation results in increased aNSCs proliferation with no change in neuronal progeny and that this hyperproliferation likely does not result solely from activation of the epidermal growth factor receptor (EGFR). Loss of LRIG1, however, also leads to impaired activation of transforming growth factor beta (TGFβ) and bone morphogenic protein (BMP) signalling. Biochemically, we show that LRIG1 binds TGFβ/BMP receptors and the TGFβ1 ligand. Finally, we show that the consequences of these interactions are to facilitate SMAD phosphorylation. Collectively, these data suggest that unlike in embryonic NSCs where EGFR may be the primary mechanism of action, in aNSCs, LRIG1 and TGFβ pathways function together to fulfill their inhibitory roles. LRIG1 is an important negative regulator of cell signaling. In this study, loss of LRIG1 leads to hyperproliferation of adult neural stem cells by facilitation of TGFβ and BMP signalling pathways. [ABSTRACT FROM AUTHOR]
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