|
|
|
|
|
|
|
||
J. Cell Biol.,
Volume 145, Number 6, June 14, 1999 1309-1324
* Fred Hutchinson Cancer Research Center, Seattle, Washington 98109; Laminin 5 regulates anchorage and motility
of epithelial cells through integrins Department of Medicine, Division of Dermatology,
University of Washington, Seattle, Washington 98198; Department of Pathobiology, University of Washington, Seattle,
Washington 98198; and § Hormone Research Center, Chonnam National University, Kwangju 500-757, South Korea
6
4 and 31, respectively. We used targeted disruption of the LAMA3
gene, which encodes the 3 subunit of laminin 5 and
other isoforms, to examine developmental functions that are regulated by adhesion to the basement membrane (BM). In homozygous null animals, profound epithelial abnormalities were detected that resulted in
neonatal lethality, consistent with removal of all 3-laminin isoforms from epithelial BMs. Alterations in
three different cellular functions were identified. First, using a novel tissue adhesion assay, we found that the
mutant BM could not induce stable adhesion by integrin 64, consistent with the presence of junctional
blisters and abnormal hemidesmosomes. In the absence
of laminin 5 function, we were able to detect a new
ligand for integrin 31 in the epidermal BM, suggesting that basal keratinocytes can utilize integrin 31 to
interact with an alternative ligand. Second, we identified a survival defect in mutant epithelial cells that
could be rescued by exogenous laminin 5, collagen, or
an antibody against integrin 64, suggesting that signaling through 1 or 4 integrins is sufficient for survival. Third, we detected abnormalities in ameloblast
differentiation in developing mutant incisors indicating
that events downstream of adhesion are affected in mutant animals. These results indicate that laminin 5 has
an important role in regulating tissue organization, gene expression, and survival of epithelium.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
