An in vivo screen for proteolytic switch domains that can mediate Notch activation by force.

• Tác giả: Amber Ajamu-Johnson, Rama F Alashqar, Frederick C Baker, Simran Bhikot, Jacob Harman, Trevor Jordan, Paul D Langridge, Gary Struhl, Breana Walton
• Ngôn ngữ: eng
• Ký hiệu phân loại: 736.94 Ice and snow
• Thông tin xuất bản: United States : bioRxiv : the preprint server for biology , 2025
• Bộ sưu tập: NCBI
• ID: 699492

Tóm tắt

UNLABELLED: Notch proteins are single pass transmembrane receptors activated by sequential extracellular and intramembrane cleavages that release their cytosolic domains to function as transcription factors in the nucleus. Upon binding, Delta/Serrate/LAG-2 (DSL) ligands activate Notch by exerting a "pulling" force across the intercellular ligand/receptor bridge. This pulling force is generated by Epsin-mediated endocytosis of ligand into the signal-sending cell, and results in the extracellular cleavage of the force-sensing Negative Regulatory Region (NRR) of the receptor by an ADAM10 protease [Kuzbanian (Kuz) in ONE SENTENCE SUMMARY: A scalable in vivo screen for Epsin and ADAM10 dependent proteolytic switches that can mediate Notch activation in response to force.