DOI: 10.1083/jcb.134.1.67. A function for filamentous alpha-smooth muscle actin: retardation of motility in fibroblasts.

A function for filamentous alpha-smooth muscle actin: retardation of motility in fibroblasts.

10.1083/jcb.134.1.67

Crossref journal-article

Rockefeller University Press

The Journal of cell biology (291)

Abstract

Actins are known to comprise six mammalian isoforms of which beta- and gamma-nonmuscle actins are present in all cells, whereas alpha-smooth muscle (alpha-sm) actin is normally restricted to cells of the smooth muscle lineages. alpha-Sm actin has been found also to be expressed transiently in certain nonmuscle cells, in particular fibroblasts, which are referred to as myofibroblasts. The functional significance of alpha-sm actin in fibroblasts is unknown. However, myofibroblasts appear to play a prominent role in stromal reaction in breast cancer, at the site of wound repair, and in fibrotic reactions. Here, we show that the presence of alpha-sm actin is a signal for retardation of migratory behavior in fibroblasts. Comparison in a migration assay of fibroblast cell strains with and without alpha-sm actin revealed migratory restraint in alpha-sm actin-positive fibroblasts. Electroporation of monoclonal antibody (mAb) 1A4, which recognizes specifically the NH2-terminal Ac-EEED sequence of alpha-sm actin, significantly increased the frequency of migrating cells over that obtained with an unrelated antibody or a mAb against beta-actin. Time-lapse video microscopy revealed migratory rates of 4.8 and 3.0 microns/h, respectively. To knock out the alpha-sm actin protein, several antisense phosphorothioate oligodeoxynucleotide (ODNs) were tested. One of these, 3'UTI, which is complementary to a highly evolutionary conserved 3' untranslated (3'UT) sequence of alpha-sm actin mRNA, was found to block alpha-sm actin synthesis completely without affecting the synthesis of any other proteins as analyzed by two-dimensional gel electrophoresis. Targeting by antisense 3'UTI significantly increased motility compared with the corresponding sense ODN. alpha-Sm actin inhibition also led to the formation of less prominent focal adhesions as revealed by immunofluorescence staining against vinculin, talin, and beta1-integrin. We propose that an important function of filamentous alpha-sm actin is to immobilize the cells.

Bibliography

RÃ¸nnov-Jessen, L., & Petersen, O. W. (1996). A function for filamentous alpha-smooth muscle actin: retardation of motility in fibroblasts. The Journal of Cell Biology, 134(1), 67â80.

Authors 2

L Rønnov-Jessen (first)
O W Petersen (additional)

References 0 Referenced 165

None

Dates

Type	When
Created	21 years, 3 months ago (May 14, 2004, 9:23 p.m.)
Deposited	2 years, 1 month ago (July 22, 2023, 2:23 a.m.)
Indexed	3 months, 1 week ago (May 20, 2025, 11:30 a.m.)
Issued	29 years, 2 months ago (July 1, 1996)
Published	29 years, 2 months ago (July 1, 1996)
Published Online	29 years, 2 months ago (July 1, 1996)
Published Print	29 years, 2 months ago (July 1, 1996)

Funders 0

None

BibTeX

@article{R_nnov_Jessen_1996, title={A function for filamentous alpha-smooth muscle actin: retardation of motility in fibroblasts.}, volume={134}, ISSN={1540-8140}, url={http://dx.doi.org/10.1083/jcb.134.1.67}, DOI={10.1083/jcb.134.1.67}, number={1}, journal={The Journal of cell biology}, publisher={Rockefeller University Press}, author={Rønnov-Jessen, L and Petersen, O W}, year={1996}, month=jul, pages={67–80} }

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