Peak BMP Responses in the Drosophila Embryo Are Dependent on the Activation of Integrin Signaling

Cell Reports
Annick SawalaHilary L Ashe

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.

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Citations

Dec 20, 2015·Cytokine & Growth Factor Reviews·Shinya MatsudaMarkus Affolter
Feb 17, 2017·Biochemical Society Transactions·Georg Sedlmeier, Jonathan P Sleeman
Dec 3, 2016·Biochemical Society Transactions·Hilary L Ashe
Jul 5, 2021·Cellular Signalling·Laura-Marie A ZimmermannGerhard Sengle
Jul 24, 2021·Cells & Development·Timothy E Saunders

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transfection

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