AMOT130 drives BMP-SMAD signaling at the apical membrane in polarized cells.
Angiomotins
Bone Morphogenetic Protein 6
/ metabolism
Bone Morphogenetic Proteins
/ metabolism
Cell Line
Cell Membrane
/ metabolism
Cell Polarity
/ physiology
Endosomes
/ metabolism
Endothelial Cells
/ metabolism
Epithelial Cells
/ metabolism
HEK293 Cells
Humans
Intercellular Signaling Peptides and Proteins
/ metabolism
MCF-7 Cells
Membrane Proteins
/ metabolism
Microfilament Proteins
/ metabolism
Phosphoproteins
/ metabolism
Phosphorylation
Signal Transduction
/ physiology
Smad Proteins
/ metabolism
Tight Junctions
/ metabolism
Journal
Molecular biology of the cell
ISSN: 1939-4586
Titre abrégé: Mol Biol Cell
Pays: United States
ID NLM: 9201390
Informations de publication
Date de publication:
15 01 2020
15 01 2020
Historique:
pubmed:
5
12
2019
medline:
18
11
2020
entrez:
5
12
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31800378
doi: 10.1091/mbc.E19-03-0179
pmc: PMC6960409
doi:
Substances chimiques
AMOT protein, human
0
Angiomotins
0
BMP6 protein, human
0
Bone Morphogenetic Protein 6
0
Bone Morphogenetic Proteins
0
Intercellular Signaling Peptides and Proteins
0
Membrane Proteins
0
Microfilament Proteins
0
Phosphoproteins
0
Smad Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
118-130Références
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