期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 79, 期 2, 页码 -出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-022-04140-5
关键词
Cell polarity; Cryptic lamellipodia; Junctional adhesion molecules; JAMs; MDCK; Tetraspanins
资金
- Projekt DEAL
- Deutsche Forschungsgemeinschaft [EB 160/7-1, SCHN 430/9-1, EXC1003-CiM FF-2016-15 JS, EXC1003-CiM FF-2016-1]
Junctional adhesion molecule (JAM)-A is a cell adhesion receptor that plays a crucial role in cell-cell contact and epithelial barrier formation. Recent studies have shown that JAM-A also regulates collective cell migration in polarized epithelial cells, and this is achieved through its interactions with α3β1 integrin, tetraspanins CD151 and CD9, which are associated with laminin and collagen-I.
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 alpha 3 beta 1 integrin. We also find that JAM-A interacts with tetraspanins CD151 and CD9, which both interact with alpha 3 beta 1 integrin and regulate alpha 3 beta 1 integrin activity in different contexts. Mapping experiments indicate that JAM-A associates with alpha 3 beta 1 integrin and tetraspanins CD151 and CD9 through its extracellular domain. Similar to depletion of JAM-A, depletion of either alpha 3 beta 1 integrin or tetraspanins CD151 and CD9 in MDCK cells slows down collective cell migration. Our findings suggest that JAM-A exists with alpha 3 beta 1 integrin and tetraspanins CD151 and CD9 in a functional complex to regulate collective cell migration of polarized epithelial cells.
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