The Fras1/Frem family of extracellular matrix proteins: structure, function, and association with Fraser syndrome and the mouse bleb phenotype.

Abstract:

:Fras1 and the structurally related proteins Frem1, Frem2, and Frem3, comprise a novel family of extracellular matrix proteins, which localize in a similar fashion underneath the lamina densa of epithelial basement membranes. They are involved in the structural adhesion of the skin epithelium to its underlying mesenchyme. Deficiency in the individual murine Fras1/Frem genes gives rise to the bleb phenotype, which is equivalent to the human hereditary disorder Fraser syndrome, characterized by cryptophthalmos (hidden eyes), embryonic skin blistering, renal agenesis, and syndactyly. Recent studies revealed a functional cooperation between the Fras1/Frem gene products, in which Fras1, Frem1 and Frem2 are simultaneously stabilized at the lowermost region of the basement membrane by forming a macromolecular ternary complex. Loss of any of these proteins results in the collapse of the protein assembly, thus providing a molecular explanation for the highly similar phenotypic defects displayed by the respective mutant mice. Here, we summarize the current knowledge regarding the structure, function, and interplay between the proteins of the Fras1/Frem family and further propose a possible scenario for the evolution of the corresponding genes.

journal_name

Connect Tissue Res

authors

Petrou P,Makrygiannis AK,Chalepakis G

doi

10.1080/03008200802148025

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

277-82

issue

3

eissn

0300-8207

issn

1607-8438

pii

795331836

journal_volume

49

pub_type

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