Intestinal Paneth cell differentiation relies on asymmetric regulation of Wnt signaling by Daam1/2

0583497 - BFÚ 2024 RIV US eng J - Článek v odborném periodiku
Colozza, G. - Lee, H. - Merenda, A. - Wu, S. S. - Catala-Bordes, A. - Radaszkiewicz, T.W. - Jordens, I. - Lee, J. H. - Bamford, A. - Farnhammer, F. - Low, T. Y. - Maurice, M. M. - Bryja, Vítězslav - Kim, J. - Koo, B.
Intestinal Paneth cell differentiation relies on asymmetric regulation of Wnt signaling by Daam1/2.
Science Advances. Roč. 9, č. 47 (2023), č. článku eadh9673. ISSN 2375-2548. E-ISSN 2375-2548
Institucionální podpora: RVO:68081707
Klíčová slova: convergent extension * wnt/beta-catenin * endocytosis * receptors * proteins * activation * growth * lgr5 * rho
Obor OECD: Biochemical research methods
Impakt faktor: 13.6, rok: 2022
Způsob publikování: Omezený přístup
https://www.science.org/doi/10.1126/sciadv.adh9673

The mammalian intestine is one of the most rapidly self-renewing tissues, driven by stem cells residing at the crypt bottom. Paneth cells form a major element of the niche microenvironment providing various growth factors to orchestrate intestinal stem cell homeostasis, such as Wnt3. Different Wnt ligands can selectively activate beta-catenin-dependent (canonical) orindependent (noncanonical) signaling. Here, we report that the Dishevelled-associated activator of morphogenesis 1 (Daam1) and its paralogue Daam2 asymmetrically regulate canonical and noncanonical Wnt (Wnt/PCP) signaling. Daam1/2 interacts with the Wnt inhibitor RNF43, and Daam1/2 double knockout stimulates canonical Wnt signaling by preventing RNF43-dependent degradation of the Wnt receptor, Frizzled (Fzd). Single-cell RNA sequencing analysis revealed that Paneth cell differentiation is impaired by Daam1/2 depletion because of defective Wnt/PCP signaling. Together, we identified Daam1/2 as an unexpected hub molecule coordinating both canonical and noncanonical Wnt, which is fundamental for specifying an adequate number of Paneth cells.
Trvalý link: https://hdl.handle.net/11104/0351470