TLR ligand-induced podosome disassembly in dendritic cells is ADAM17 dependent

TY - JOUR

T1 - TLR ligand-induced podosome disassembly in dendritic cells is ADAM17 dependent

AU - West, Michele A.

AU - Prescott, Alan R.

AU - Chan, Kui Ming

AU - Zhou, Zhongjun

AU - Rose-John, Stefan

AU - Scheller, Juergen

AU - Watts, Colin

PY - 2008/9/8

Y1 - 2008/9/8

N2 - Toll-like receptor (TLR) signaling induces a rapid reorganization of the actin cytoskeleton in cultured mouse dendritic cells (DC), leading to enhanced antigen endocytosis and a concomitant loss of filamentous actin-rich podosomes. We show that as podosomes are lost, TLR signaling induces prominent focal contacts and a transient reduction in DC migratory capacity in vitro. We further show that podosomes in mouse DC are foci of pronounced gelatinase activity, dependent on the enzyme membrane type I matrix metalloprotease (MT1-MMP), and that DC transiently lose the ability to degrade the extracellular matrix after TLR signaling. Surprisingly, MMP inhibitors block TLR signaling-induced podosome disassembly, although stimulated endocytosis is unaffected, which demonstrates that the two phenomena are not obligatorily coupled. Podosome disassembly caused by TLR signaling occurs normally in DC lacking MT1-MMP, and instead requires the tumor necrosis factor alpha-converting enzyme ADAM17 (a disintegrin and metalloprotease 17), which demonstrates a novel role for this "sheddase" in regulating an actin-based structure.

AB - Toll-like receptor (TLR) signaling induces a rapid reorganization of the actin cytoskeleton in cultured mouse dendritic cells (DC), leading to enhanced antigen endocytosis and a concomitant loss of filamentous actin-rich podosomes. We show that as podosomes are lost, TLR signaling induces prominent focal contacts and a transient reduction in DC migratory capacity in vitro. We further show that podosomes in mouse DC are foci of pronounced gelatinase activity, dependent on the enzyme membrane type I matrix metalloprotease (MT1-MMP), and that DC transiently lose the ability to degrade the extracellular matrix after TLR signaling. Surprisingly, MMP inhibitors block TLR signaling-induced podosome disassembly, although stimulated endocytosis is unaffected, which demonstrates that the two phenomena are not obligatorily coupled. Podosome disassembly caused by TLR signaling occurs normally in DC lacking MT1-MMP, and instead requires the tumor necrosis factor alpha-converting enzyme ADAM17 (a disintegrin and metalloprotease 17), which demonstrates a novel role for this "sheddase" in regulating an actin-based structure.

KW - MHC CLASS-II

KW - EXTRACELLULAR-MATRIX DEGRADATION

KW - ANTIGEN PRESENTATION

KW - CROSS-PRESENTATION

KW - PLASMA-MEMBRANE

KW - TNF-ALPHA

KW - IN-VITRO

KW - MATURATION

KW - MIGRATION

KW - METALLOPROTEINASE

UR - https://www.scopus.com/pages/publications/51649088232

U2 - 10.1083/jcb.200801022

DO - 10.1083/jcb.200801022

M3 - Article

C2 - 18762577

SN - 0021-9525

VL - 182

SP - 993

EP - 1005

JO - Journal of Cell Biology

JF - Journal of Cell Biology

IS - 5

ER -