Recognition of the neural chemoattractant Netrin-1 by integrins alpha6beta4 and alpha3beta1 regulates epithelial cell adhesion and migration.
Netrins, axon guidance cues in the CNS, have also been detected in epithelial tissues. In this study, using the embryonic pancreas as a model system, we show that Netrin-1 is expressed in a discrete population of epithelial cells, localizes to basal membranes, and specifically associates with elements of the extracellular matrix. We demonstrate that alpha6beta4 integrin mediates pancreatic epithelial cell adhesion to Netrin-1, whereas recruitment of alpha6beta4 and alpha3beta1 regulate the migration of CK19+/PDX1+ putative pancreatic progenitors on Netrin-1. These results provide evidence for the activation of epithelial cell adhesion and migration by a neural chemoattractant, and identify Netrin-1/integrin interactions as adhesive/guidance cues for epithelial cells.
Department of Pediatrics, The Whittier Institute for Diabetes, University of California, San Diego, La Jolla, CA 92037, USA.
Mayra
M
Yebra
Anthony M P
AM
Montgomery
Giuseppe R
GR
Diaferia
Thomas
T
Kaido
Steve
S
Silletti
Brandon
B
Perez
Margaret L
ML
Just
Simone
S
Hildbrand
Rosemary
R
Hurford
Elin
E
Florkiewicz
Marc
M
Tessier-Lavigne
Vincenzo
V
Cirulli
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D039201:Integrin alpha3beta1 / Q000378:metabolism*; D039161:Integrin alpha6beta4 / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism*; D000075388:Netrin-1; D010179:Pancreas / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D016326:Extracellular Matrix Proteins; D039201:Integrin alpha3beta1; D039161:Integrin alpha6beta4; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; D010446:Peptide Fragments; D021122:Protein Subunits; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1