Junctional adhesion molecule-A regulates cell migration and resistance to shear stress.
Junctional adhesion molecule-A (JAM-A) is an adhesive protein expressed in endothelial cells, epithelial cells, platelets, and some leukocytes. JAM-A localizes to the tight junctions between contacting endothelial and epithelial cells, where it contributes to cell-cell adhesion and to the control of paracellular permeability. JAM-A also regulates cell motility, even though the quantitative biophysical features have not been characterized. In this study, we evaluated the role of JAM-A in the regulation of cell motility using JAM-A-expressing and JAM-A-deficient murine endothelial cells. We report that, in the absence of shear stress, JAM-A absence increases cell motility by increasing directional persistence but not cell speed. In addition, in the presence of shear stress, JAM-A absence increases protrusion extension in the direction of flow and increased downstream cellular displacement (while, conversely, decreasing upstream displacement). All these effects of JAM-A absence are mitigated by the microtubule-stabilizing compound taxol. A motility- and microtubule-related function, integrin-mediated adhesiveness, was only slightly reduced in JAM-A-deficient cells compared with JAM-A-expressing cells. However, overexpression of JAM-A in the JAM-A-deficient cells increased integrin adhesiveness to the same levels as those observed in taxol-treated JAM-A-deficient cells. Taken together, these data indicate that JAM-A regulates cell motility by cooperating with microtubule-stabilizing pathways.
Huang
Hayden
H
Cardiovascular Division, Brigham and Women's Hospital, Cambridge, Massachusetts 02139, USA. hhuang@rics.bwh.harvard.edu
Cruz
Francisco
F
Bazzoni
Gianfranco
G
D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement; D022081:Cell Surface Extensions; D042783:Endothelial Cells; D019012:Integrin beta1 / Q000378:metabolism; D016023:Integrins / Q000502:physiology; D051379:Mice; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D015815:Cell Adhesion Molecules; C498686:F11r protein, mouse; D019012:Integrin beta1; D016023:Integrins; D011956:Receptors, Cell Surface