Embryonic stem cells are devoid of macropinocytosis, a trafficking pathway for activin A in differentiated cells

Nikoleta Kostopoulou; Sofia Bellou; Eleni Bagli; Maria Markou; Eleftherios Kostaras; Marko Hyvönen; Yiannis Kalaidzidis; Angelos Papadopoulos; Varvara Chalmantzi; Athena Kyrkou; Ekaterini Panopoulou; Theodore Fotsis; Carol Murphy

doi:10.1242/jcs.246892

Embryonic stem cells are devoid of macropinocytosis, a trafficking pathway for activin A in differentiated cells

J Cell Sci. 2021 Jul 1;134(13):jcs246892. doi: 10.1242/jcs.246892. Epub 2021 Jul 12.

Authors

Nikoleta Kostopoulou¹, Sofia Bellou^{1

2}, Eleni Bagli¹, Maria Markou^{1

3}, Eleftherios Kostaras^{1

3}, Marko Hyvönen⁴, Yiannis Kalaidzidis⁵, Angelos Papadopoulos^{1

6}, Varvara Chalmantzi^{1

6}, Athena Kyrkou¹, Ekaterini Panopoulou³, Theodore Fotsis^{1

3}, Carol Murphy^{1

6

7}

Affiliations

¹ Foundation for Research & Technology-Hellas (FORTH), Institute of Molecular Biology and Biotechnology (IMBB), Department of Biomedical Research, Ioannina, 45110, Greece.
² Confocal Laser Scanning Microscopy Unit, Network of Research Supporting Laboratories, University of Ioannina, Ioannina, 45110, Greece.
³ Laboratory of Biological Chemistry, University of Ioannina Medical School, Ioannina, 45110, Greece.
⁴ Department of Biochemistry, University of Cambridge, Cambridge, CB2 1TN, UK.
⁵ Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
⁶ School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
⁷ Centre of Membrane Proteins and Receptors, University of Birmingham, A118 Aston Webb, Edgbaston, Birmingham, B15 2TT, UK.

PMID: 34313314
DOI: 10.1242/jcs.246892

Abstract

Ligand-receptor complexes formed at the plasma membrane are internalised via various endocytic pathways that influence the ultimate signalling output by regulating the selection of interaction partners by the complex along the trafficking route. We report that, in differentiated cells, activin A-receptor complexes are internalised via clathrin-mediated endocytosis (CME) and macropinocytosis (MP), whereas in human embryonic stem cells (hESCs) internalisation occurs via CME. We further show that hESCs are devoid of MP, which becomes functional upon differentiation towards endothelial cells through mesoderm mediators. Our results reveal, for the first time, that MP is an internalisation route for activin A in differentiated cells, and that MP is not active in hESCs and is induced as cells differentiate.

Keywords: Activin A; Endothelial cells; Human embryonic stem cells; Macropinocytosis; Receptor trafficking; Signalling.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Activins*
Cell Differentiation
Embryonic Stem Cells
Endocytosis
Endothelial Cells*
Humans

Substances

activin A
Activins