Lamellipodium extension and cadherin adhesion: two cell responses to cadherin activation relying on distinct signalling pathways.
Cell adhesion molecules of the cadherin family contribute to the regulation of cell shape and fate by mediating strong intercellular adhesion through Ca2+-dependent interaction of their ectodomain and association of their cytoplasmic tail to actin. However, the mechanisms co-ordinating cadherinmediated adhesion with the reorganization of the actin cytoskeleton remain elusive. Here, the formation of de novo contacts was dissected by spreading cells on a highly active N-cadherin homophilic ligand. Cells responded to N-cadherin activation by extending lamellipodium and organizing cadherin-catenin complexes and actin filaments in cadherin adhesions. Lamellipodium protrusion, associated with actin polymerization at the leading edge sustained the extension of cadherin contacts through a phosphoinositide 3-kinase (PI 3-kinase)-Rac1 pathway. Cadherin adhesions were formed by PI 3-kinase-independent, Rac1-dependent co-recruitment of adhesion complexes and actin filaments. The expression and localization of p120 at the plasma membrane, associated with an increase in membrane-associated Rac1 was required for both cell responses, consistent with a major role of p120 in signalling pathways initiated by cadherin activation and contributing to Rac1-dependent contact extension and maturation. These results provide additional information on the mechanisms by which cadherin coordinates adhesion with dynamic changes in the cytoskeleton to control cell shape and intercellular junction organization.
Gavard
Julie
J
Signalisation et Différenciation Cellulaires dans les Systèmes Nerveux et Musculaire, U440 INSERM-UPMC, Institut du Fer à Moulin, 17 rue du Fer à Moulin, 75005 Paris, France.
Lambert
Mireille
M
Grosheva
Inna
I
Marthiens
Véronique
V
Irinopoulou
Theano
T
Riou
Jean-François
JF
Bershadsky
Alexander
A
Mège
René-Marc
RM
D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D051177:Catenins; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D048429:Cell Size; D002478:Cells, Cultured; D002645:Chickens; D003599:Cytoskeleton / Q000378:metabolism; D007365:Intercellular Junctions / Q000502:physiology*; D051379:Mice; D008856:Microscopy, Fluorescence; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011554:Pseudopodia / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013347:Subcellular Fractions; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D000095002:Delta Catenin
D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D010750:Phosphoproteins; D019869:Phosphatidylinositol 3-Kinases; D020830:rac1 GTP-Binding Protein; D000095002:Delta Catenin