The Extracellular Matrix Receptor Discoidin Domain Receptor 1 Regulates Collagen Transcription by Translocating to the Nucleus
Abstract
The receptor discoidin domain receptor 1 (DDR1) is activated by collagen, upregulated in injured kidneys, and contributes to kidney fibrosis, but how DDR1 controls fibrosis is poorly understood. The authors show that upon collagen stimulation, DDR1 translocates to the nucleus. To do this, DDR1 must bind with SEC61B, a component of the Sec61 translocon, as well as with nonmuscle myosin IIA and β-actin. In the nucleus, DDR1 binds to chromatin to increase the transcription of collagen IV, a major collagen upregulated in fibrosis. The study reveals a novel mechanism whereby collagen-activated DDR1 moves to the nucleus to increase the production of profibrotic molecules.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 05, 2019
- Source ID
- 10.1681/asn.2018111160
Entities
People
- Agnes B. Fogo
- Ambra Pozzi
- Billy G. Hudson
- Corina M. Borza
- Hong-jun Liao
- Manuel Chiusa
- Mark P. de Caestecker
- Ming-zhi Zhang
- Nataliya I. Skrypnyk
- Roberto M. Vanacore
- Roy Zent
- Su Yan
- Trayambak Basak
- Vadim Pedchenko
- Wen Hu
- Xiyue Li
Organizations
- National Institutes of Health
- United States Department of Defense
- United States Department of Veterans Affairs
- Vanderbilt University Medical Center