TY - JOUR
T1 - Geometry sensing by dendritic cells dictates spatial organization and PGE(2)-induced dissolution of podosomes
AU - van den Dries, Koen
AU - van Helden, Suzanne F G
AU - te Riet, Joost
AU - Diez-Ahedo, Ruth
AU - Manzo, Carlo
AU - Oud, Machteld M
AU - van Leeuwen, Frank N
AU - Brock, Roland
AU - Garcia-Parajo, Maria F
AU - Cambi, Alessandra
AU - Figdor, Carl G
PY - 2012/6
Y1 - 2012/6
N2 - Assembly and disassembly of adhesion structures such as focal adhesions (FAs) and podosomes regulate cell adhesion and differentiation. On antigen-presenting dendritic cells (DCs), acquisition of a migratory and immunostimulatory phenotype depends on podosome dissolution by prostaglandin E(2) (PGE(2)). Whereas the effects of physico-chemical and topographical cues have been extensively studied on FAs, little is known about how podosomes respond to these signals. Here, we show that, unlike for FAs, podosome formation is not controlled by substrate physico-chemical properties. We demonstrate that cell adhesion is the only prerequisite for podosome formation and that substrate availability dictates podosome density. Interestingly, we show that DCs sense 3-dimensional (3-D) geometry by aligning podosomes along the edges of 3-D micropatterned surfaces. Finally, whereas on a 2-dimensional (2-D) surface PGE(2) causes a rapid increase in activated RhoA levels leading to fast podosome dissolution, 3-D geometric cues prevent PGE(2)-mediated RhoA activation resulting in impaired podosome dissolution even after prolonged stimulation. Our findings indicate that 2-D and 3-D geometric cues control the spatial organization of podosomes. More importantly, our studies demonstrate the importance of substrate dimensionality in regulating podosome dissolution and suggest that substrate dimensionality plays an important role in controlling DC activation, a key process in initiating immune responses.
AB - Assembly and disassembly of adhesion structures such as focal adhesions (FAs) and podosomes regulate cell adhesion and differentiation. On antigen-presenting dendritic cells (DCs), acquisition of a migratory and immunostimulatory phenotype depends on podosome dissolution by prostaglandin E(2) (PGE(2)). Whereas the effects of physico-chemical and topographical cues have been extensively studied on FAs, little is known about how podosomes respond to these signals. Here, we show that, unlike for FAs, podosome formation is not controlled by substrate physico-chemical properties. We demonstrate that cell adhesion is the only prerequisite for podosome formation and that substrate availability dictates podosome density. Interestingly, we show that DCs sense 3-dimensional (3-D) geometry by aligning podosomes along the edges of 3-D micropatterned surfaces. Finally, whereas on a 2-dimensional (2-D) surface PGE(2) causes a rapid increase in activated RhoA levels leading to fast podosome dissolution, 3-D geometric cues prevent PGE(2)-mediated RhoA activation resulting in impaired podosome dissolution even after prolonged stimulation. Our findings indicate that 2-D and 3-D geometric cues control the spatial organization of podosomes. More importantly, our studies demonstrate the importance of substrate dimensionality in regulating podosome dissolution and suggest that substrate dimensionality plays an important role in controlling DC activation, a key process in initiating immune responses.
KW - Cell Adhesion
KW - Cell Communication
KW - Cell Differentiation
KW - Cell Movement
KW - Cells, Cultured
KW - Dendritic Cells/cytology
KW - Dinoprostone/physiology
KW - Focal Adhesions
KW - Humans
KW - Surface Properties
KW - rhoA GTP-Binding Protein/metabolism
U2 - 10.1007/s00018-011-0908-y
DO - 10.1007/s00018-011-0908-y
M3 - Article
C2 - 22204022
VL - 69
SP - 1889
EP - 1901
JO - Cellular and Molecular Life Sciences : CMLS
JF - Cellular and Molecular Life Sciences : CMLS
SN - 1420-682X
IS - 11
ER -