Hemostatic, inflammatory, and fibroblast responses are blunted in mice lacking gelsolin.
Gelsolin, an 82 kDa actin-binding protein, has potent actin filament-severing activity in vitro. To investigate the in vivo function of gelsolin, transgenic gelsolin-null (Gsn-) mice were generated and found to have normal embryonic development and longevity. However, platelet shape changes are decreased in Gsn- mice, causing prolonged bleeding times. Neutrophil migration in vivo into peritoneal exudates and in vitro is delayed. Gsn- dermal fibroblasts have excessive actin stress fibers and migrate more slowly than wild-type fibroblasts, but have increased contractility in vitro. These observations establish the requirement of gelsolin for rapid motile responses in cell types involved in stress responses such as hemostasis, inflammation, and wound healing. Neither gelsolin nor other proteins with similar actin filament-severing activity are expressed in early embryonic cells, indicating that this mechanism of actin filament dynamics is not essential for motility during early embryogenesis.
Witke
W
W
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Sharpe
A H
AH
Hartwig
J H
JH
Azuma
T
T
Stossel
T P
TP
Kwiatkowski
D J
DJ
D000199:Actins / Q000502:physiology; D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D002465:Cell Movement; D002478:Cells, Cultured; D005333:Fetus / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D018260:Gelsolin / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006487:Hemostasis / Q000502:physiology; D007249:Inflammation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000502:physiology; D009504:Neutrophils / Q000166:cytology; D012333:RNA, Messenger / Q000032:analysis; D013234:Stem Cells / Q000502:physiology; D014945:Wound Healing / Q000502:physiology
D000199:Actins; D018260:Gelsolin; D012333:RNA, Messenger