The CD157-integrin partnership controls transendothelial migration and adhesion of human monocytes
Autor: | Nicola Lo Buono, Giulia Nacci, Simona Morone, Erika Ortolan, Alona Inzhutova, Alberto L Horenstein, Ada Funaro, R. Parrotta, Enza Ferrero, Paola Bovino |
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Jazyk: | angličtina |
Rok vydání: | 2011 |
Předmět: |
Cell signaling
Integrin ectoenzyme Biology GPI-Linked Proteins Biochemistry Cell Line Extracellular matrix Focal adhesion Phosphatidylinositol 3-Kinases Membrane Microdomains Antigens CD Cell Movement CD157 Cell Adhesion Humans cell signaling ADP-ribosyl Cyclase Antibodies Blocking Cell adhesion inflammation monocytes intergins Molecular Biology Integrin beta1 Endothelial Cells Fibrinogen Cell migration Cell Biology Extracellular Matrix Fibronectins Cell biology Fibronectin CD18 Antigens biology.protein Signal transduction Protein Kinases Signal Transduction |
Popis: | CD157, a member of the CD38 gene family, is an NAD-metabolizing ectoenzyme and a signaling molecule whose role in polarization, migration, and diapedesis of human granulocytes has been documented; however, the molecular events underpinning this role remain to be elucidated. This study focused on the role exerted by CD157 in monocyte migration across the endothelial lining and adhesion to extracellular matrix proteins. The results demonstrated that anti-CD157 antibodies block monocyte transmigration and adhesion to fibronectin and fibrinogen but that CD157 cross-linking is sufficient to overcome the block, suggesting an active signaling role for the molecule. Consistent with this is the observation that CD157 is prevalently located within the detergent-resistant membrane microdomains to which, upon clustering, it promotes the recruitment of β(1) and β(2) integrin, which, in turn, leads to the formation of a multimolecular complex favoring signal transduction. This functional cross-talk with integrins allows CD157 to act as a receptor despite its intrinsic structural inability to do so on its own. Intracellular signals mediated by CD157 rely on the integrin/Src/FAK (focal adhesion kinase) pathway, resulting in increased activity of the MAPK/ERK1/2 and the PI3K/Akt downstream signaling pathways, which are crucial in the control of monocyte transendothelial migration. Collectively, these findings indicate that CD157 acts as a molecular organizer of signaling-competent membrane microdomains and that it forms part of a larger molecular machine ruled by integrins. The CD157-integrin partnership provides optimal adhesion and transmigration of human monocytes. |
Databáze: | OpenAIRE |
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