Cis-interactions between Notch and its ligands block ligand-independent Notch activity

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Abstract

The Notch pathway is integrated into numerous developmental processes and therefore is fine-tuned on many levels, including receptor production, endocytosis, and degradation. Notch is further characterized by a two-fold relationship with its Delta-Serrate (DSL) ligands, as ligands from opposing cells (trans-ligands) activate Notch, whereas ligands expressed in the same cell (cis-ligands) inhibit signaling. We show that cells without both cis and trans ligands are able to mediate Notch-dependent developmental events during Drosophila oogenesis, indicating ligand-independent Notch activity occurs when the receptor is free of cis and trans ligands. Furthermore, cis-ligands can reduce Notch activity in endogenous and genetically-induced situations of elevated trans-ligand-independent Notch signaling. We conclude that cis-expressed ligands exert their repressive effect on Notch signaling in cases of trans-ligand independent activation, and propose a new function of cis-inhibition which buffers cells against accidental Notch activity.

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William Hunt Palmer

Department of Biological Science, Florida State University, Tallahassee, United States

Competing interests
The authors declare that no competing interests exist.
Dongyu Jia

Department of Biological Science, Florida State University, Tallahassee, United States

Competing interests
The authors declare that no competing interests exist.
Wu-Min Deng

Department of Biological Science, Florida State University, Tallahassee, United States

For correspondence
wumin@bio.fsu.edu

Competing interests
The authors declare that no competing interests exist.

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