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

Autor:	Sawala A; Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK., Scarcia M; Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK., Sutcliffe C; Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK., Wilcockson SG; Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK., Ashe HL; Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK. Electronic address: hilary.ashe@manchester.ac.uk.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2015 Sep 08; Vol. 12 (10), pp. 1584-93. Date of Electronic Publication: 2015 Aug 28.
DOI:	10.1016/j.celrep.2015.08.012
Abstrakt:	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. (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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