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

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 Lr...

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Bibliographic Details
Published in:	Communications biology Vol. 7; no. 1; pp. 845 - 13
Main Authors:	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.
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 10-07-2024 Nature Publishing Group Nature Portfolio
Subjects:	13/100 13/106 13/51 13/95 45/91 631/378/340 631/378/368/2431 64/60 Adult Stem Cells - metabolism Animals Biomedical and Life Sciences Bone growth Bone morphogenetic proteins Bone Morphogenetic Proteins - metabolism Cell Proliferation Cell signaling Epidermal growth factor receptors ErbB Receptors - genetics ErbB Receptors - metabolism Growth factors Life Sciences Membrane Glycoproteins - genetics Membrane Glycoproteins - metabolism Mice Mice, Knockout Nerve Tissue Proteins Neural stem cells Neural Stem Cells - cytology Neural Stem Cells - metabolism Phosphorylation Receptor mechanisms Signal Transduction Smad protein Stem cells Subventricular zone Transforming Growth Factor beta - metabolism Transforming growth factor-b1
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Summary:	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 (TGF β ) and bone morphogenic protein (BMP) signalling. Biochemically, we show that LRIG1 binds TGF β /BMP receptors and the TGF β 1 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 TGF β 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 TGF β and BMP signalling pathways.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2399-3642 2399-3642
DOI:	10.1038/s42003-024-06524-8