2024-01-18 カロリンスカ研究所(KI)
◆通常、Notchは隣接する細胞の引っ張りによって機械的に活性化されると考えられていましたが、研究者たちはJag1というタンパク質をDNAオリガミに組み込んでNotchを必要に応じて活性化できることを発見しました。これにより、Notchシグナリング経路の理解が深まり、発がんなどの病気に対する新しいアプローチが開かれる可能性があります。
<関連情報>
- https://news.ki.se/dna-construction-led-to-unexpected-discovery-of-important-cell-function
- https://www.nature.com/articles/s41467-023-44059-4
可溶性で多価のJag1 DNA折り紙ナノパターンが、引っ張る力なしにノッチを活性化することを発見 Soluble and multivalent Jag1 DNA origami nanopatterns activate Notch without pulling force
Ioanna Smyrlaki,Ferenc Fördős,Iris Rocamonde-Lago,Yang Wang,Boxuan Shen,Antonio Lentini,Vincent C. Luca,Björn Reinius,Ana I. Teixeira & Björn Högberg
Nature Communications Published:18 January 2024
DOI:https://doi.org/10.1038/s41467-023-44059-4
Abstract
The Notch signaling pathway has fundamental roles in embryonic development and in the nervous system. The current model of receptor activation involves initiation via a force-induced conformational change. Here, we define conditions that reveal pulling force-independent Notch activation using soluble multivalent constructs. We treat neuroepithelial stem-like cells with molecularly precise ligand nanopatterns displayed from solution using DNA origami. Notch signaling follows with clusters of Jag1, and with chimeric structures where most Jag1 proteins are replaced by other binders not targeting Notch. Our data rule out several confounding factors and suggest a model where Jag1 activates Notch upon prolonged binding without appearing to need a pulling force. These findings reveal a distinct mode of activation of Notch and lay the foundation for the development of soluble agonists.
