Regulation of endothelial cell adhesion by profilin.
BACKGROUND
Although profilin is believed to be an essential regulator of the actin cytoskeleton in most cells, its precise role in mammalian cells remains unknown. We have used replication-incompetent adenovirus carrying the human profilin I cDNA as a means rapidly to increase the concentration of profilin in human aortic endothelial cells 12-31-fold above baseline--levels never before achieved in mammalian cells.


RESULTS
The concentration of filamentous actin was not detectably affected by profilin overexpression. Actin stress fibers were, however, absent from areas of high profilin content in overexpressing cells, and the bulk of filaments was located at the periphery of the cells. We observed a gradient in the distribution of overexpressed profilin in migrating endothelial cells, with most profilin molecules concentrated near the advancing edge where focal contacts are being formed and focal adhesion proteins are located. Profilin overexpression resulted in increased recruitment of fibronectin receptors to the plasma membrane. Adhesion of endothelial cells to fibronectin was markedly and selectively increased by profilin overexpression.


CONCLUSIONS
We conclude that an important role for profilin in mammalian cells may be its contribution to the formation of focal contacts, particularly those involving the fibronectin receptor.
Moldovan
N I
NI
Department of Neurosciences, Case Western Reserve University School of Medicine, 10900 Euclid Ave., Cleveland, Ohio 44106-4975, USA.
Milliken
E E
EE
Irani
K
K
Chen
J
J
Sohn
R H
RH
Finkel
T
T
Goldschmidt-Clermont
P J
PJ
D000199:Actins / Q000032:analysis / Q000502:physiology; D000256:Adenoviridae / Q000235:genetics; D001011:Aorta; D002448:Cell Adhesion / Q000502:physiology*; D003285:Contractile Proteins; D003599:Cytoskeleton / Q000502:physiology; D004727:Endothelium / Q000737:chemistry / Q000166:cytology* / Q000502:physiology; D015967:Gene Expression Regulation, Viral; D006801:Humans; D008840:Microfilament Proteins / Q000032:analysis / Q000502:physiology*; D051304:Profilins
D000199:Actins; D003285:Contractile Proteins; D008840:Microfilament Proteins; C495738:PFN1 protein, human; D051304:Profilins