JAM-A interacts with α3β1 integrin and tetraspanins CD151 and CD9 to regulate collective cell migration of polarized epithelial cells.

Junctional adhesion molecule (JAM)-A is a cell adhesion receptor localized at epithelial cell-cell contacts with enrichment at the tight junctions. Its role during cell-cell contact formation and epithelial barrier formation has intensively been studied. In contrast, its role during collective cell migration is largely unexplored. Here, we show that JAM-A regulates collective cell migration of polarized epithelial cells. Depletion of JAM-A in MDCK cells enhances the motility of singly migrating cells but reduces cell motility of cells embedded in a collective by impairing the dynamics of cryptic lamellipodia formation. This activity of JAM-A is observed in cells grown on laminin and collagen-I but not on fibronectin or vitronectin. Accordingly, we find that JAM-A exists in a complex with the laminin- and collagen-I-binding α3β1 integrin. We also find that JAM-A interacts with tetraspanins CD151 and CD9, which both interact with α3β1 integrin and regulate α3β1 integrin activity in different contexts. Mapping experiments indicate that JAM-A associates with α3β1 integrin and tetraspanins CD151 and CD9 through its extracellular domain. Similar to depletion of JAM-A, depletion of either α3β1 integrin or tetraspanins CD151 and CD9 in MDCK cells slows down collective cell migration. Our findings suggest that JAM-A exists with α3β1 integrin and tetraspanins CD151 and CD9 in a functional complex to regulate collective cell migration of polarized epithelial cells.

Thölmann S ，Seebach J ，Otani T ，Florin L ，Schnittler H ，Gerke V ，Furuse M ，Ebnet K ... -  《-》

The CD9/CD81 tetraspanin complex and tetraspanin CD151 regulate α3β1 integrin-dependent tumor cell behaviors by overlapping but distinct mechanisms.

Gustafson-Wagner E ，Stipp CS 《PLoS One》

Tetraspanin CD151 regulates glycosylation of (alpha)3(beta)1 integrin.

Baldwin G ，Novitskaya V ，Sadej R ，Pochec E ，Litynska A ，Hartmann C ，Williams J ，Ashman L ，Eble JA ，Berditchevski F ... -  《JOURNAL OF BIOLOGICAL CHEMISTRY》

Tetraspanin CD9 links junctional adhesion molecule-A to αvβ3 integrin to mediate basic fibroblast growth factor-specific angiogenic signaling.

Peddibhotla SS ，Brinkmann BF ，Kummer D ，Tuncay H ，Nakayama M ，Adams RH ，Gerke V ，Ebnet K ... -  《-》

CD151 promotes α3β1 integrin-dependent organization of carcinoma cell junctions and restrains collective cell invasion.

Zevian SC ，Johnson JL ，Winterwood NE ，Walters KS ，Herndon ME ，Henry MD ，Stipp CS ... -  《-》