Impaired T lymphocyte trafficking in mice deficient in an actin-nucleating protein, mDia1.
Trafficking of immune cells is controlled by directed migration of relevant cells toward chemotactic signals. Actin cytoskeleton undergoes continuous remodeling and serves as machinery for cell migration. The mDia family of formins and the Wiskott-Aldrich syndrome protein (WASP)-Arp2/3 system are two major actin nucleating-polymerizing systems in mammalian cells, with the former producing long straight actin filaments and the latter producing branched actin meshwork. Although much is known about the latter, the physiological functions of mDia proteins are unclear. We generated mice deficient in one mDia isoform, mDia1. Although mDia1(-/-) mice were born and developed without apparent abnormality, mDia1(-/-) T lymphocytes exhibited impaired trafficking to secondary lymphoid organs in vivo and showed reduced chemotaxis, little actin filament formation, and impaired polarity in response to chemotactic stimuli in vitro. Similarly, mDia1(-/-) thymocytes showed reduced chemotaxis and impaired egression from the thymus. These results suggest that mDia1 plays a distinct role in chemotaxis in T lymphocyte trafficking.
Department of Pharmacology,Kyoto University Faculty of Medicine, Kyoto 606-8501, Japan.
Daiji
D
Sakata
Hiroyuki
H
Taniguchi
Shingo
S
Yasuda
Aki
A
Adachi-Morishima
Yoko
Y
Hamazaki
Rika
R
Nakayama
Takashi
T
Miki
Nagahiro
N
Minato
Shuh
S
Narumiya
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D018925:Chemokines / Q000494:pharmacology; D000080865:Formins; D007111:Immunity, Cellular / Q000187:drug effects; D008221:Lymphoid Tissue / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology
D000199:Actins; D002352:Carrier Proteins; D018925:Chemokines; C491464:Diap1 protein, mouse; D000080865:Formins