Abstract
Within a 3D tissue, cells need to integrate signals from growth factors, such as BMPs, and the extracellular matrix (ECM) to coordinate growth and differentiation. Here, we use the Drosophila embryo as a model to investigate how BMP responses are influenced by a cell's local ECM environment. We show that integrins, which are ECM receptors, are absolutely required for peak BMP signaling. This stimulatory effect of integrins requires their intracellular signaling function, which is activated by the ECM protein collagen IV. Mechanistically, integrins interact with the BMP receptor and stimulate phosphorylation of the downstream Mad transcription factor. The BMP-pathway-enhancing function of integrins is independent of focal adhesion kinase, but it requires conserved NPXY motifs in the β-integrin cytoplasmic tail. Furthermore, we show that an α-integrin subunit is a BMP target gene, identifying positive feedback between integrin signaling and BMP pathway activity that may contribute to robust cell fate decisions.
References
Dec 1, 1992·The Journal of Cell Biology·V M ParalkarA H Reddi
Nov 8, 1991·Science·T E O'TooleM H Ginsberg
Feb 10, 1989·Cell·M LeptinM Wilcox
Mar 25, 1999·Genes & Development·M D Martin-Bermudo, N H Brown
Aug 14, 1999·Science·F G Giancotti, E Ruoslahti
Aug 11, 2000·Matrix Biology : Journal of the International Society for Matrix Biology·N H Brown
Feb 13, 2001·Genes & Development·C RushlowN Kirov
Mar 12, 2003·Genes & Development·Frieder Schöck, Norbert Perrimon
Jul 2, 2003·Development·Helena AraujoEthan Bier
Aug 7, 2004·Science·Dave KosmanEthan Bier
Mar 11, 2005·Nature·Yu-Chiun Wang, Edwin L Ferguson
Mar 16, 2007·Journal of Cell Science·Weibin ShiXu Cao
Sep 22, 2007·Journal of Cellular Physiology·Naved AlamLucia R Languino
Jan 26, 2008·Microscopy Research and Technique·Jamshid KhoshnoodiBilly G Hudson
Feb 26, 2009·Genes & Development·Kyle R LegateReinhard Fässler
Dec 8, 2009·Science·Richard O Hynes
Feb 18, 2010·Developmental Cell·David M UmulisHans G Othmer
Aug 17, 2010·Developmental Cell·Stephanie BuntHelen Skaer
Jan 8, 2011·Science·Saori L Haigo, David Bilder
Jun 27, 2012·Proceedings of the National Academy of Sciences of the United States of America·Annick SawalaHilary L Ashe
Jul 17, 2012·Current Biology : CB·Coert MargadantArnoud Sonnenberg
Sep 4, 2012·The EMBO Journal·Hongyu TianGerard C Blobe
Feb 8, 2013·Journal of Thrombosis and Haemostasis : JTH·J ZhouJ-J Chiu
Nov 5, 2013·Current Biology : CB·Jackie Gavin-SmythEdwin L Ferguson
Feb 3, 2015·ELife·Jennifer WinstanleyHilary L Ashe
Citations
Dec 20, 2015·Cytokine & Growth Factor Reviews·Shinya MatsudaMarkus Affolter
Mar 29, 2019·Nature·Stefan MünsterPavel Tomancak
Feb 17, 2017·Biochemical Society Transactions·Georg Sedlmeier, Jonathan P Sleeman
Dec 3, 2016·Biochemical Society Transactions·Hilary L Ashe
Aug 13, 2020·Bioengineering·John TysonC LaShan Simpson
Feb 1, 2020·Haematologica·Sandrine JeanpierreSylvain Lefort
Jul 17, 2020·Acta Biomaterialia·Julius Sefkow-WernerElisa Migliorini
Jul 5, 2021·Cellular Signalling·Laura-Marie A ZimmermannGerhard Sengle
Jul 24, 2021·Cells & Development·Timothy E Saunders