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Updated: May 17, 2026

Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
Regulation of ligand-independent Notch signal through intracellular trafficking
Kazuya Hori1, Anindya Sen, Tom Kirchhausen
1Department of Cell Biology; Harvard Medical School; Boston, MA USA.
Abstract:
Notch signaling is an evolutionarily conserved mechanism that defines a key cell fate control mechanism in metazoans. Notch signaling relies on the surface interaction between the Notch receptor and membrane bound ligands in an apposing cell. In our recent study,(22) we uncover a non-canonical receptor activation path that relies on a ligand-independent, intracellular activation of the receptor as it travels through the endosomal compartments. We found that Notch receptor, targeted for degradation lysosomal degradation through multivesicular bodies (MVBs) is "diverted" toward activation upon mono-ubiquitination through a synergy between the ubiquitin ligase Deltex, the non-visual β-arrestin Kurtz and the ESCRT-III component Shrub. This activation path is not universal but appears to depend on the cellular context.
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