Amoeboid T lymphocytes Require the Septin Cytoskeleton for Cortical Integrity and Persistent Motility

The systems that refine actomyosin forces during motility remain poorly understood. Septins assemble on the T cell cortex and are enriched at the mid-zone in filaments. Septin knockdown causes membrane blebbing, excess leading edge protrusions, and lengthening of the trailingedge uropod. The associated loss of rigidity permits motility, but cells become uncoordinated and poorly persistent. This also relieves a previously unrecognized restriction to migration through small pores. Pharmacologically rigidifying cells counteracts this effect, and relieving cytoskeletal rigidity synergizes with septin-depletion. These data suggest that septins tune actomyosin forces during motility, and likely regulate lymphocyte trafficking in confined tissues.