Septin filaments crosslink actin stress fibers to promote focal adhesion maturation and cell migration, Dolat et al. reveal.
During normal development and tumor metastasis, epithelial cells undergo an epithelial-to-mesenchymal transition (EMT) that loosens their contacts with neighboring cells and enhances cell motility. At the front of migrating mesenchymal cells, radial actin stress fibers transduce force from contractile actin filaments (known as transverse arcs) at the top of the cell to the focal adhesions that attach the cell to the underlying extracellular matrix, promoting adhesion maturation and cell motility. Dolat et al. investigated the potential role of another cytoskeletal element, the filaments formed by the septin family of GTPases, which are often overexpressed in renal cell carcinomas.
The researchers found that septin filaments interweave with transverse arcs and radial actin stress fibers at the front of migrating kidney epithelial cells. Knocking down septins disrupted the actin network’s organization and inhibited the maturation of focal adhesions. This phenotype could be rescued by overexpressing the actin-bundling protein α-actinin, suggesting that septin filaments serve to cross-link actin stress fibers. Indeed, Dolat et al. found that septin 9 could bundle actin filaments in vitro.
Septin 9 was up-regulated in kidney cells undergoing EMT. Overexpressing this septin enhanced cell migration, whereas knocking down septic 9 impeded cell motility. Senior author Elias Spiliotis now wants to determine how septins cross-link actin filaments and to investigate what governs their localization and assembly in the leading edge of migrating epithelia.
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Text by Ben Short
