Caveolin‐1 influences epithelial collective cell migration via FMNL2 formin

• Published in: Biology of the cell 2021-02, Vol.113 (2), p.107-117
• Main Authors: Katsuno‐Kambe, Hiroko, Parton, Robert G., Yap, Alpha S., Teo, Jessica L.
• Format: Article
• Language: English
• Subjects: Caveolae; Caveolin‐1; Epithelial migration; FMNL2; Formin
• ISSN: 0248-4900; 1768-322X
• DOI: 10.1111/boc.202000116

Background Information Epithelial collective cell migration requires the intrinsic locomotor activity of cells to be coordinated across populations. This coordination is governed by the presence of cell–cell adhesions as well as the cooperative behaviour of cells within the monolayer. Results Here, we report a role for Caveolin‐1 (CAV1) in epithelial collective cell migration. CAV1 depletion reduced the migratory behaviour of AML12 liver epithelial cells when grown as monolayers, but not as individual cells. This suggested that CAV1 is a component of the process by which multicellular collectivity regulates epithelial motility. The correlation length for migration velocity was increased by CAV1 RNAi, a possible sign of epithelial jamming. However, CAV1 RNAi reduced migration, even when monolayers were allowed to migrate into unconfined spaces. The migratory defect was ameliorated by simultaneous depletion of the FMNL2 formin, whose cortical recruitment is increased in CAV1 RNAi cells. Conclusions We therefore suggest that CAV1 modulates intraepithelial motility by controlling the cortical availability of FMNL2. Significance Although epithelial collective cell migration has been observed in multiple contexts both in vivo and in vitro, the inherent coupling and coordination of activity between cells within the monolayer remain incompletely understood. Our study highlights a role for CAV1 in regulating intraepithelial motility, an effect that involves the formin FMNL2. Research article: This study reveals how Caveolin 1 (CAV1) can regulate the speed and behaviour of epithelial cell migration. Loss of CAV1 results in (1) reduction of monolayer motility and (2) the emergence of larger cooperative groups of cells within the monolayer. Of note, loss of CAV1 leads to enhanced recruitment of the FMNL2 formin to cell junctions. Down‐regulation of FMNL2 in CAV1 knockdown monolayers restored monolayer speed and coordination. Hence, CAV1 can modulate monolayer motility and behaviour by regulating junctional FMNL2.