title: The CD157-integrin partnership controls transendothelial migration and adhesion of human monocytes.
abstract: 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.
authors.affiliation: Laboratory of Immunogenetics, Department of Genetics, University of Torino Medical School, 10126 Torino, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Lo Buono
authors.forename: Rossella
authors.initials: R
authors.lastname: Parrotta
authors.forename: Simona
authors.initials: S
authors.lastname: Morone
authors.forename: Paola
authors.initials: P
authors.lastname: Bovino
authors.forename: Giulia
authors.initials: G
authors.lastname: Nacci
authors.forename: Erika
authors.initials: E
authors.lastname: Ortolan
authors.forename: Alberto L
authors.initials: AL
authors.lastname: Horenstein
authors.forename: Alona
authors.initials: A
authors.lastname: Inzhutova
authors.forename: Enza
authors.initials: E
authors.lastname: Ferrero
authors.forename: Ada
authors.initials: A
authors.lastname: Funaro
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019138:Antibodies, Blocking / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D018821:CD18 Antigens / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D005340:Fibrinogen / Q000235:genetics / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D021962:Membrane Microdomains / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D019138:Antibodies, Blocking; D015703:Antigens, CD; D018821:CD18 Antigens; D005353:Fibronectins; D058851:GPI-Linked Proteins; D019012:Integrin beta1; D005340:Fibrinogen; D011494:Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D036541:ADP-ribosyl Cyclase; C087521:ADP-ribosyl cyclase 2