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

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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Author(s)

  • Michele A. West
  • Alan R. Prescott
  • Zhongjun Zhou
  • Stefan Rose-John
  • Jürgen Scheller
  • Colin Watts

Detail(s)

Original languageEnglish
Pages (from-to)993-1005
Journal / PublicationJournal of Cell Biology
Volume182
Issue number5
Publication statusPublished - 8 Sep 2008
Externally publishedYes

Abstract

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 α-converting enzyme ADAM17 (a disintegrin and metalloprotease 17), which demonstrates a novel role for this "sheddase" in regulating an actin-based structure. © 2008 West et al.

Citation Format(s)

TLR ligand-induced podosome disassembly in dendritic cells is ADAM17 dependent. / West, Michele A.; Prescott, Alan R.; Kui, Ming Chan; Zhou, Zhongjun; Rose-John, Stefan; Scheller, Jürgen; Watts, Colin.

In: Journal of Cell Biology, Vol. 182, No. 5, 08.09.2008, p. 993-1005.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal