Control of endothelial cell polarity and sprouting angiogenesis by non-centrosomal microtubules
Abstract
Microtubules control different aspects of cell polarization. In cells with a radial microtubule system, a pivotal role in setting up asymmetry is attributed to the relative positioning of the centrosome and the nucleus. Here, we show that centrosome loss had no effect on the ability of endothelial cells to polarize and move in 2D and 3D environments. In contrast, non-centrosomal microtubules stabilized by the microtubule minus-end-binding protein CAMSAP2 were required for directional migration on 2D substrates and for the establishment of polarized cell morphology in soft 3D matrices. CAMSAP2 was also important for persistent endothelial cell sprouting during in vivo zebrafish vessel development. In the absence of CAMSAP2, cell polarization in 3D could be partly rescued by centrosome depletion, indicating that in these conditions the centrosome inhibited cell polarity. We propose that CAMSAP2-protected non-centrosomal microtubules are needed for establishing cell asymmetry by enabling microtubule enrichment in a single cell protrusion.
Article and author information
Author details
Funding
European Research Council (Synergy 609822)
- Anna Akhmanova
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (ALW Open Program grant 824.15.017)
- Anna Akhmanova
Marie Sklodowska-Curie Actions (IEF fellowship)
- Maud Martin
China Scholarship Council (PhD fellowship)
- Jingchao Wu
Fonds De La Recherche Scientifique - FNRS (FRIA fellowship)
- Alexandra Veloso
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal experiments were approved by the animal welfare committee of the University of Liege (protocol number 14-1556, laboratory agreement number LA 1610002).
Copyright
© 2018, Martin et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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