title: ANKS1B Interacts with the Cerebral Cavernous Malformation Protein-1 and Controls Endothelial Permeability but Not Sprouting Angiogenesis.
abstract: Cerebral cavernous malformations are fragile blood vessel conglomerates in the central nervous system that are caused by mutations in the CCM1/KRIT1, CCM2 or CCM3 genes. The gene products form a protein complex at adherens junctions and loss of either CCM protein disrupts endothelial cell quiescence leading to increased permeability and excessive angiogenesis. We performed a yeast 2-hybrid screen to identify novel proteins directly interacting with KRIT1. The ankyrin repeat and sterile alpha motif domain-containing protein 1B (ANKS1B) was identified as a novel binding partner of KRIT1. Silencing of ANKS1B or the related gene ANKS1A in primary human endothelial cells had no significant effects on cellular proliferation, migration and sprouting angiogenesis. However, silencing of ANKS1B expression disturbed endothelial cell barrier functions leading to increased permeability. Forced ANKS1B expression reduced permeability. This was independent of Rho kinase activity and the presence of KRIT1. Taken together, ANKS1B was identified as a novel KRIT1-interacting protein that selectively controls endothelial permeability but not angiogenesis.
authors.affiliation: Vascular Signaling and Cancer (A270), German Cancer Research Center (DKFZ-ZMBH Alliance), D-69120, Heidelberg, Germany.|Vascular Biology and Tumor Angiogenesis, Medical Faculty Mannheim (CBTM), Heidelberg University, D-68167, Mannheim, Germany.
authors.forename: Stefanie E
authors.initials: SE
authors.lastname: Herberich
authors.affiliation: Vascular Signaling and Cancer (A270), German Cancer Research Center (DKFZ-ZMBH Alliance), D-69120, Heidelberg, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Klose
authors.affiliation: Vascular Signaling and Cancer (A270), German Cancer Research Center (DKFZ-ZMBH Alliance), D-69120, Heidelberg, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Moll
authors.affiliation: Vascular Signaling and Cancer (A270), German Cancer Research Center (DKFZ-ZMBH Alliance), D-69120, Heidelberg, Germany.
authors.forename: Wan-Jen
authors.initials: WJ
authors.lastname: Yang
authors.affiliation: Vascular Signaling and Cancer (A270), German Cancer Research Center (DKFZ-ZMBH Alliance), D-69120, Heidelberg, Germany.|Vascular Biology and Tumor Angiogenesis, Medical Faculty Mannheim (CBTM), Heidelberg University, D-68167, Mannheim, Germany.
authors.forename: Joycelyn
authors.initials: J
authors.lastname: Wüstehube-Lausch
authors.affiliation: Vascular Signaling and Cancer (A270), German Cancer Research Center (DKFZ-ZMBH Alliance), D-69120, Heidelberg, Germany.|Vascular Biology and Tumor Angiogenesis, Medical Faculty Mannheim (CBTM), Heidelberg University, D-68167, Mannheim, Germany.|Department of Medicine I and Clinical Chemistry, Heidelberg University Hospital, D-69120, Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Fischer
mesh_terms: D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002463:Cell Membrane Permeability / Q000502:physiology*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D000075927:KRIT1 Protein; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C489945:ANKS1B protein, human; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger