Uncoupling integrin adhesion and signaling: the betaPS cytoplasmic domain is sufficient to regulate gene expression in the Drosophila embryo.
Integrin cell surface receptors are ideally suited to coordinate cellular differentiation and tissue assembly during embryogenesis, as they can mediate both signaling and adhesion. We show that integrins regulate gene expression in the intact developing embryo by identifying two genes that require integrin function for their normal expression in Drosophila midgut endodermal cells. We determined the relative roles of integrin adhesion versus signaling in the regulation of these integrin target genes. We find that integrin-mediated adhesion is not required between the endodermal cells and the surrounding visceral mesoderm for integrin target gene expression. In addition, a chimeric protein that lacks integrin-adhesive function, but maintains the ability to signal, can substitute for the endogenous integrin and regulate integrin target genes. This chimera consists of an oligomeric extracellular domain fused to the integrin betaPS subunit cytoplasmic domain; a control monomeric extracellular domain fusion does not alter integrin target gene expression. Therefore, oligomerization of the 47-amino-acid betaPS intracellular domain is sufficient to initiate a signaling pathway that regulates gene expression in the developing embryo.
Martin-Bermudo
M D
MD
Wellcome Trust/Cancer Research Campaign Institute of Cancer and Developmental Biology, and Department of Anatomy, University of Cambridge, Cambridge CB2 1QR, UK.
Brown
N H
NH
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion / Q000502:physiology*; D003593:Cytoplasm / Q000378:metabolism; D017931:DNA Primers; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins; D004707:Endoderm / Q000166:cytology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D039001:Integrin alpha Chains; D016023:Integrins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008648:Mesoderm / Q000166:cytology; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D017931:DNA Primers; D029721:Drosophila Proteins; D039001:Integrin alpha Chains; D016023:Integrins; D011993:Recombinant Fusion Proteins; C082188:if protein, Drosophila