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.
Highlights
Cell polarization is a prerequisite for virtually every specialized cellular process
Using 2D monolayer wound healing assay, we confirmed the anterior position of the centrosome and the Golgi apparatus in migrating endothelial cells (ECs) and extended this observation to tip ECs sprouting from a spheroid in 3D (Figure 1—figure supplement 1A)
Previous work showed that the MT minus-end binding protein CAMSAP2 is a key player in the regulation of non-centrosomal MT minus ends in mammalian cells (Akhmanova and Hoogenraad, 2015; Jiang et al, 2014; Tanaka et al, 2012; Yau et al, 2014)
Summary
Cell polarization is a prerequisite for virtually every specialized cellular process. Microtubules (MTs) are thought to support cell polarity by forming an asymmetrical network (Etienne-Manneville, 2013). Depleting CAMSAP2 prevented the normal formation of blood vessels in zebrafish embryos Taken together, these findings change our understanding of how microtubules affect cell movement and how important the centrosome is for this process. The process of new blood vessel development, endothelial cells (ECs) respond to external cues by coordinating numerous activities, including proliferation, sprouting, migration, lumen formation and anastomosis (Geudens and Gerhardt, 2011; Potente et al, 2011). Detailed analysis showed that non-centrosomal MTs are required to allow MT redistribution in a single-cell protrusion and enable polarized trafficking, directional stabilization of protrusions and persistent migration
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