A crucial role for 2 integrins in podosome formation, dynamics and Toll-like-receptor-signaled disassembly in dendritic cells

Gawden-Bone, C., West, M.A., Morrison, V.L. , Edgar, A.J., McMillan, S.J., Dill, B.D., Trost, M., Prescott, A., Fagerholm, S.C. and Watts, C. (2014) A crucial role for 2 integrins in podosome formation, dynamics and Toll-like-receptor-signaled disassembly in dendritic cells. Journal of Cell Science, 127(19), pp. 4213-4224. (doi:10.1242/jcs.151167) (PMID:25086067) (PMCID:PMC4179490)

Gawden-Bone, C., West, M.A., Morrison, V.L. , Edgar, A.J., McMillan, S.J., Dill, B.D., Trost, M., Prescott, A., Fagerholm, S.C. and Watts, C. (2014) A crucial role for 2 integrins in podosome formation, dynamics and Toll-like-receptor-signaled disassembly in dendritic cells. Journal of Cell Science, 127(19), pp. 4213-4224. (doi:10.1242/jcs.151167) (PMID:25086067) (PMCID:PMC4179490)

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Abstract

The dynamic properties of podosomes, their ability to degrade the underlying matrix and their modulation by Toll-like receptor (TLR) signaling in dendritic cells (DCs) suggests they have an important role in migration. Integrins are thought to participate in formation and dynamics of podosomes but the multiplicity of integrins in podosomes has made this difficult to assess. We report that murine DCs that lack β2 integrins fail to form podosomes. Re-expression of β2 integrins restored podosomes but not when the membrane proximal or distal NPxF motifs, or when an intervening triplet of threonine residues were mutated. We show that β2 integrins are remarkably long-lived in podosome clusters and form a persistent framework that hosts multiple actin-core-formation events at the same or adjacent sites. When β2 integrin amino acid residues 745 or 756 were mutated from Ser to Ala, podosomes became resistant to dissolution mediated through TLR signaling. TLR signaling did not detectably modulate phosphorylation at these sites but mutation of either residue to phospho-mimetic Asp increased β2 integrin turnover in podosomes, indicating that phosphorylation at one or both sites establishes permissive conditions for TLR-signaled podosome disassembly.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Morrison, Dr Vicky
Authors: Gawden-Bone, C., West, M.A., Morrison, V.L., Edgar, A.J., McMillan, S.J., Dill, B.D., Trost, M., Prescott, A., Fagerholm, S.C., and Watts, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Cell Science
Publisher:The Company of Biologists Ltd.
ISSN:1477-9137
ISSN (Online):0021-9533
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in Journal of Cell Science 127(19):4213-4224
Publisher Policy:Reproduced under a Creative Commons License

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