title: IQ domain GTPase-activating protein 1 is involved in shear stress-induced progenitor-derived endothelial cell alignment.
abstract: Shear stress is one of mechanical constraints which are exerted by blood flow on endothelial cells (ECs). To adapt to shear stress, ECs align in the direction of flow through adherens junction (AJ) remodeling. However, mechanisms regulating ECs alignment under shear stress are poorly understood. The scaffold protein IQ domain GTPase activating protein 1 (IQGAP1) is a scaffold protein which couples cell signaling to the actin and microtubule cytoskeletons and is involved in cell migration and adhesion. IQGAP1 also plays a role in AJ organization in epithelial cells. In this study, we investigated the potential IQGAP1 involvement in the endothelial cells alignment under shear stress. Progenitor-derived endothelial cells (PDECs), transfected (or not) with IQGAP1 small interfering RNA, were exposed to a laminar shear stress (1.2 N/m(2)) and AJ proteins (VE-cadherin and β-catenin) and IQGAP1 were labeled by immunofluorescence. We show that IQGAP1 is essential for ECs alignment under shear stress. We studied the role of IQGAP1 in AJs remodeling of PDECs exposed to shear stress by studying cell localization and IQGAP1 interactions with VE-cadherin and β-catenin by immunofluorescence and Proximity Ligation Assays. In static conditions, IQGAP1 interacts with VE-cadherin but not with β-catenin at the cell membrane. Under shear stress, IQGAP1 lost its interaction from VE-cadherin to β-catenin. This "switch" was concomitant with the loss of β-catenin/VE-cadherin interaction at the cell membrane. This work shows that IQGAP1 is essential to ECs alignment under shear stress and that AJ remodeling represents one of the mechanisms involved. These results provide a new approach to understand ECs alignment under to shear stress.
authors.affiliation: Bioingénierie Tissulaire, Université de Bordeaux, U 1026, F-33000 Bordeaux, France ; Bioingénierie Tissulaire, U1026, INSERM, Bordeaux, France.
authors.forename: Lila
authors.initials: L
authors.lastname: Rami
authors.forename: Patrick
authors.initials: P
authors.lastname: Auguste
authors.forename: Noélie B
authors.initials: NB
authors.lastname: Thebaud
authors.forename: Reine
authors.initials: R
authors.lastname: Bareille
authors.forename: Richard
authors.initials: R
authors.lastname: Daculsi
authors.forename: Jean
authors.initials: J
authors.lastname: Ripoche
authors.forename: Laurence
authors.initials: L
authors.lastname: Bordenave
mesh_terms: D022005:Adherens Junctions / Q000502:physiology; D015703:Antigens, CD / Q000378:metabolism; D001483:Base Sequence; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D020868:Gene Silencing; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism*; D013314:Stress, Mechanical; D051176:beta Catenin / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D034741:RNA, Small Interfering; D051176:beta Catenin; D020703:ras GTPase-Activating Proteins; D000099152:Cadherin 5; C101203:IQ motif containing GTPase activating protein 1