title: The Formin FMNL3 Controls Early Apical Specification in Endothelial Cells by Regulating the Polarized Trafficking of Podocalyxin.
abstract: Angiogenesis is the fundamental process by which new blood vessels form from pre-existing vasculature. It plays a critical role in the formation of the vasculature during development and is triggered in response to tissue hypoxia in adult organisms. This process requires complex and coordinated regulation of the endothelial cell cytoskeleton to control cell shape and polarity. In our previous work, we showed that the cytoskeletal regulator FMNL3/FRL2 controls the alignment of stabilized microtubules during polarized endothelial cell elongation and that depletion of FMNL3 retards elongation of the intersegmental vessels in zebrafish. Recent work has shown that FMNL3 is also needed for vascular lumen formation, a critical element of the formation of functional vessels. Here, we show that FMNL3 interacts with Cdc42 and RhoJ, two Rho family GTPases known to be required for lumen formation. FMNL3 and RhoJ are concentrated at the early apical surface, or AMIS, and regulate the formation of radiating actin cables from this site. In diverse biological systems, formins mediate polarized trafficking through the generation of similar actin filaments tracks. We show that FMNL3 and RhoJ are required for polarized trafficking of podocalyxin to the early apical surface--an important event in vascular lumenogenesis.
authors: School of Biochemistry, Medical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK.
authors: Mark
authors: M
authors: Richards
authors: School of Biochemistry, Medical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK.
authors: Clare
authors: C
authors: Hetheridge
authors: School of Biochemistry, Medical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK. Electronic address: h.mellor@bristol.ac.uk.
authors: Harry
authors: H
authors: Mellor
mesh_terms: D003599:Cytoskeleton / Q000502:physiology; D005347:Fibroblasts; D000080865:Formins; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000235:genetics* / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C476209:FMNL3 protein, human; D000080865:Formins; D008565:Membrane Proteins; D011506:Proteins; D012795:Sialoglycoproteins; C001643:podocalyxin; C417188:RHOJ protein, human; D020764:cdc42 GTP-Binding Protein; D020741:rho GTP-Binding Proteins