Biophysics of Notch Signaling

Notch signaling is a conserved system of communication between adjacent cells, influencing numerous cell fate decisions in the development of multicellular organisms. Aberrant signaling is also implicated in many human pathologies. At its core, Notch has a mechanotransduction module that decodes rec...

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Bibliographic Details
Published in:Annual review of biophysics 2021-05, Vol.50 (1), p.157-189
Main Authors: Sprinzak, David, Blacklow, Stephen C
Format: Article
Language:English
Subjects:
Animals
Biophysical Phenomena
Cell Nucleus - metabolism
Humans
intramembrane proteolysis
mechanotransduction
Notch signaling
Receptors, Notch - chemistry
Receptors, Notch - genetics
Receptors, Notch - metabolism
Signal Transduction
structural biology
transcription
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Summary:Notch signaling is a conserved system of communication between adjacent cells, influencing numerous cell fate decisions in the development of multicellular organisms. Aberrant signaling is also implicated in many human pathologies. At its core, Notch has a mechanotransduction module that decodes receptor-ligand engagement at the cell surface under force to permit proteolytic cleavage of the receptor, leading to the release of the Notch intracellular domain (NICD). NICD enters the nucleus and acts as a transcriptional effector to regulate expression of Notch-responsive genes. In this article, we review and integrate current understanding of the detailed molecular basis for Notch signal transduction, highlighting quantitative, structural, and dynamic features of this developmentally central signaling mechanism. We discuss the implications of this mechanistic understanding for the functionality of the signaling pathway in different molecular and cellular contexts.
ISSN:1936-122X
1936-1238
DOI:10.1146/annurev-biophys-101920-082204