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PMID: 19043408 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Amoeboid T lymphocytes require the septin cytoskeleton for cortical integrity and persistent motility.

Nature cell biology ·Vol. 11 ·No. 1 ·2009-01-00 ·Pages 17-26

Tooley AJ, Gilden J, Jacobelli J, Beemiller P, Trimble WS, Kinoshita M, Krummel MF

Abstract

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.

MeSH Terms
Actins/metabolism Animals Cell Membrane/metabolism,ultrastructure Cell Movement/physiology Cell Shape/physiology Cell Surface Extensions/metabolism,ultrastructure Cells, Cultured Chemotaxis, Leukocyte/physiology Cytoskeletal Proteins/genetics,metabolism Cytoskeleton/metabolism Down-Regulation/genetics GTP Phosphohydrolases/genetics,metabolism Mice Mice, Transgenic Myosins/metabolism RNA Interference Septins Stress, Mechanical T-Lymphocytes/metabolism,ultrastructure
Chemicals
Actins Cytoskeletal Proteins Sept1 protein, mouse GTP Phosphohydrolases Septins Myosins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Tooley Aaron J
The Department of Pathology, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0511, USA.
Gilden Julia
Jacobelli Jordan
Beemiller Peter
Trimble William S
Kinoshita Makoto
Krummel Matthew F
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38 references, click to expand
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Article Info
Journal
Nature cell biology
Abbr.
Nat Cell Biol
ISSN
1476-4679
DOI
10.1038/ncb1808
Published
2009-01-00
Epub
2008-00-30
Pages
17-26
Language
English
Region
England
NLM ID
100890575
PMCID
PMC3777658
Subset
IM
Grants
NIAID NIH HHS · R21 AI062899 · United States
NIAID NIH HHS · R01 AI052116 · United States
NIAID NIH HHS · R21 AI062899-02 · United States
NIAID NIH HHS · R01 AI052116-06A2 · United States
NIAID NIH HHS · R21-AI062899 · United States
Corrections
CommentIn
PMID: 19122592
External Links
PubMed source DOI: 10.1038/ncb1808 PMC Full Text View journal details
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