alpha1beta1-integrin engagement to distinct laminin-1 domains orchestrates spreading, migration and survival of neural crest cells through independent signaling pathways.
Integrin engagement regulates cell adhesion, shape, migration, growth, and differentiation, but molecular mechanisms coordinating these functions in cells remain unclear. Because of their migratory and differentiation potential, neural crest cells constitute a powerful paradigm to address this question. Here, we describe that laminin-1, a major component of their migration routes, promotes crest cell spreading, migration and survival through two distinct integrin-binding domains that are situated on both sides of its alpha1 subunit and can be separated in the LN-1 elastase proteolytic fragments E1' and E8. Interaction with either domain was mediated by the same integrin alpha1beta1 but produced distinct, complementary responses through specific signaling cascades. FAK activation upon E8 binding induced spreading, formation of actin bundles and focal adhesions, stimulated oriented migration, but failed to support survival. Conversely, Erk activation upon E1' binding promoted long-term survival and random migration without actin reorganization. Consistent with this, interaction with laminin-5 or laminin-10/11, which do not harbor integrin-binding domains in the N-terminal side of their alpha chains, failed to support survival. Thus, the signaling activity and function of integrins might depend on binding domains in their ligands, thereby revealing ligand control of integrin function as a possible mechanism for the modulation and coordination of cell response to adhesive signals.
Desban
Nathalie
N
Laboratoire de Biologie du Développement, CNRS et Université Pierre et Marie Curie, 9 quai Saint-Bernard, 75252 Paris Cedex 05, France.
Lissitzky
Jean-Claude
JC
Rousselle
Patricia
P
Duband
Jean-Loup
JL
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D048430:Cell Shape; D002470:Cell Survival; D002478:Cells, Cultured; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D039222:Integrin alpha1beta1 / Q000378:metabolism*; D007797:Laminin / Q000737:chemistry / Q000378:metabolism*; D009432:Neural Crest / Q000166:cytology*; D010196:Pancreatic Elastase / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000502:physiology*
D004791:Enzyme Inhibitors; D039222:Integrin alpha1beta1; D007797:Laminin; D010446:Peptide Fragments; D020033:Protein Isoforms; C121346:laminin 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D010196:Pancreatic Elastase