The membrane-bound Notch regulator Mnr supports Notch cleavage an signaling activity in Drosophila melanogaster

Nagel AC, Müller D, Zimmermann M, Preiss A (2021)


Publication Type: Journal article, Online publication

Publication year: 2021

Journal

URI: https://www.mdpi.com/2218-273X/11/11/1672

DOI: 10.3390/biom11111672

Open Access Link: https://www.mdpi.com/2218-273X/11/11/1672

Abstract

The Notch signaling pathway is pivotal to cellular differentiation. Activation of this pathway involves proteolysis of the Notch receptor and the release of the biologically active Notch intracellular domain, acting as a transcriptional co-activator of Notch target genes. While the regulation of Notch signaling dynamics at the level of ligand–receptor interaction, endocytosis, and transcriptional regulation has been well studied, little is known about factors influencing Notch cleavage. We identified EP555 as a suppressor of the Notch antagonist Hairless (H). EP555 drives expression of CG32521 encoding membrane-bound proteins, which we accordingly rename membrane-bound Notch regulator (mnr). Within the signal-receiving cell, upregulation of Mnr stimulates Notch recSuppleptor activation, whereas a knockdown reduces it, without apparent influence on ligand–receptor interaction. We provide evidence that Mnr plays a role in γ-secretase-mediated intramembrane cleavage of the Notch receptor. As revealed by a fly-eye-based reporter system, γ-secretase activity is stimulated by the overexpression of Mnr, and is inhibited by its knockdown. We conclude that Mnr proteins support Notch signaling activity by fostering the cleavage of the Notch receptor. With Mnr, we identified a membrane-bound factor directly augmenting Notch intra-membrane processing, thereby acting as a positive regulator of Notch signaling activity.

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How to cite

APA:

Nagel, A.C., Müller, D., Zimmermann, M., & Preiss, A. (2021). The membrane-bound Notch regulator Mnr supports Notch cleavage an signaling activity in Drosophila melanogaster. Biomolecules. https://dx.doi.org/10.3390/biom11111672

MLA:

Nagel, Anja Christina, et al. "The membrane-bound Notch regulator Mnr supports Notch cleavage an signaling activity in Drosophila melanogaster." Biomolecules (2021).

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