title: Exocyst complex component 3-like 2 (EXOC3L2) associates with the exocyst complex and mediates directional migration of endothelial cells.
abstract: The exocyst is a protein complex that ensures spatial targeting of exocytotic vesicles to the plasma membrane. We present microarray data obtained from differentiating mouse embryonic stem cell cultures that identify an up-regulation of exocyst complex component 3-like 2 (exoc3l2) mRNA in sprouting blood vessels. Vascular expression of exoc3l2 is confirmed by qPCR analysis of different mouse tissues and immunofluorescence analyses of mouse brain sections. We detect an up-regulation of exoc3l2 mRNA synthesis in primary human endothelial cells in response to VEGFA, and this response is enhanced when the cells are grown on a three-dimensional collagen I matrix. Myc-tagged EXOC3L2 co-precipitates with the exocyst protein EXOC4, and immunofluorescence detection of EXOC3L2 shows partial subcellular colocalization with EXOC4 and EXOC7. Finally, we show that exoc3l2 silencing inhibits VEGF receptor 2 phosphorylation and VEGFA-directed migration of cultured endothelial cells.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Husargatan 3, P. O. Box 582, SE-751 23, Uppsala, Sweden.
authors.forename: Irmeli
authors.initials: I
authors.lastname: Barkefors
authors.forename: Peder Fredlund
authors.initials: PF
authors.lastname: Fuchs
authors.forename: Johan
authors.initials: J
authors.lastname: Heldin
authors.forename: Tobias
authors.initials: T
authors.lastname: Bergström
authors.forename: Karin
authors.initials: K
authors.lastname: Forsberg-Nilsson
authors.forename: Johan
authors.initials: J
authors.lastname: Kreuger
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D020868:Gene Silencing; D006801:Humans; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D033921:Vesicular Transport Proteins; C467480:vascular endothelial growth factor A, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2