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 trailing-edge 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 probably regulate lymphocyte trafficking in confined tissues.
Tooley
Aaron J
AJ
The Department of Pathology, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0511, USA.
Gilden
Julia
J
Jacobelli
Jordan
J
Beemiller
Peter
P
Trimble
William S
WS
Kinoshita
Makoto
M
Krummel
Matthew F
MF
D000199:Actins / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002465:Cell Movement / Q000502:physiology*; D048430:Cell Shape / Q000502:physiology*; D022081:Cell Surface Extensions / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009218:Myosins / Q000378:metabolism; D034622:RNA Interference; D058112:Septins; D013314:Stress, Mechanical; D013601:T-Lymphocytes / Q000378:metabolism* / Q000648:ultrastructure
D000199:Actins; D003598:Cytoskeletal Proteins; C491457:Sept1 protein, mouse; D020558:GTP Phosphohydrolases; D058112:Septins; D009218:Myosins