Biophysics of Notch Signaling

David Sprinzak, Stephen C. Blacklow

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)157-189
Number of pages33
JournalAnnual Review of Biophysics
Volume50
DOIs
StatePublished - 6 May 2021

Keywords

  • Notch signaling
  • intramembrane proteolysis
  • mechanotransduction
  • signal transduction
  • structural biology
  • transcription

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