Laminin isoforms: biological roles and effects on the intracellular distribution of nuclear proteins in intestinal epithelial cells.
Laminins are structurally and functionally major components of the extracellular matrix. Four isoforms of laminins (laminin-1, -2, -5 and -10) are expressed in a specific pattern along the crypt-villus axis of the intestine. Previous works indicated that expression of these isoforms is developmentally regulated and that laminins could modulate the behaviour of intestinal cells, but the exact role of each isoform remained unclear. Here, we report the first systematic analysis of the cellular functions of the four isoforms using the human colon adenocarcinoma Caco2/TC7 cell line as a model. We compared the respective abilities of each isoform to modulate adhesion, proliferation and differentiation of intestinal epithelial cells. We found that the isoforms were functionally distinct, with laminin-10 being the most adhesive substratum, laminin-2, laminin-5 and laminin-10 enhancing cellular proliferation and at the opposite, laminin-1 stimulating intestinal cell differentiation. To begin to characterise the molecular events induced by the different isoforms, we examined by immunofluorescence the intracellular distribution of several nuclear proteins, recently highlighted by a nuclear proteomic approach. We observed clear nucleocytoplasmic redistribution of these proteins, which depended on the laminin isoform. These results provide evidence for a distinct functional role of laminins in intestinal cell functions characterised by specific localisation of nuclear proteins.
Turck
Natacha
N
INSERM, Unit 381, 67200 Strasbourg, France.
Gross
Isabelle
I
Gendry
Patrick
P
Stutzmann
Jeanne
J
Freund
Jean-Noël
JN
Kedinger
Michèle
M
Simon-Assmann
Patricia
P
Launay
Jean-François
JF
D001483:Base Sequence; D018938:Caco-2 Cells; D002448:Cell Adhesion; D002454:Cell Differentiation; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism
D018076:DNA, Complementary; D007797:Laminin; D009687:Nuclear Proteins; D020033:Protein Isoforms; C121346:laminin 1; C119013:laminin 10