The large isoform of the transmembrane protein angiomotin (AMOT130) controls cell proliferation and migration of many cell types. AMOT130 associates to the actin cytoskeleton and regulates tight-junction maintenance and signaling often via endosomal uptake of polarity proteins at tight junctions. AMOT130 is highly polarized and present only at the apical side of polarized cells. Here we show that bone morphogenetic protein (BMP) growth factor signaling and AMOT function are interlinked in apical-basal polarized cells. BMP6 controls AMOT internalization and endosomal trafficking in epithelial cells. AMOT130 interacts with the BMP receptor BMPR2 and facilitates SMAD activation and target gene expression. We further demonstrate that this effect of AMOT on BMP-SMAD signaling is dependent on endocytosis and specific to the apical side of polarized epithelial and endothelial cells. Knockdown of AMOT reduces SMAD signaling only from the apical side of polarized cells, while basolateral BMP-SMAD signaling is unaffected. This allows for the first time interference with BMP signaling in a polarized manner and identifies AMOT130 as a novel BMP signaling regulator.
-
Supplemental MaterialsMetrics
Downloads & Citations
Downloads: 179History Submitted: 27 March 2019Revised: 30 October 2019Accepted: 29 November 2019
Information © 2020 Brunner et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
Financial support was provided by the Deutsche Forschungsgemeinschaft (DFG) to P.K., J.J., and P.B. (Berlin School of Integrative Oncology; Berlin-Brandenburg School for Regenerative Therapies). Further support was provided by the SFB958 and by the Bundesministerium fuer Bildung und Forschung (BMBF) (PrevOP/OVERLOAD) to P.K. We thank Slobodan Vukicevic (University of Zagreb, Croatia) for providing recombinant BMP6, Walter Sebald (Julius-Maximilans-Universität, Würzburg, Germany) for providing recombinant BMP, Simone Spuler (Charité University Medical School, Berlin, Germany) for providing human myoblasts, and Lars Holmgren (Karolinska Institutet, Stockholm, Sweden) for the AMOT TLE antibody. We acknowledge the assistance of the Core Facility BioSupraMol supported by the DFG. We also thank Gina Dörpholz for valuable input.
Loading ...



