Abstract
Podosomes, important structures for adhesion and extracellular matrix degradation, are claimed to be involved in cell migration. In addition, podosomes are also reported to be of importance in tissue remodelling, e.g., in osteoclast-mediated bone resorption. Podosomes are highly dynamic actin-filament scaffolds onto which proteins important for their function, such as matrix metallo-proteases and integrins, attach. The dynamics of the podosomes require the action of many proteins regulating actin assembly and disassembly. One such protein, gelsolin, which associates to podosomes, has been reported to be important for podosome formation and function in osteoclasts. However, podosome-like structures have been reported in gelsolin-deficient dendritic cells, but the identity of these structures was not confirmed, and their dynamics and function was not investigated. Like many other cells, dendritic cells of the immune system also form matrix degrading podosomes. In the present study, we show that dendritic cells form podosomes independently of gelsolin, that there are no major alterations in their dynamics of formation and disassembly, and that they exhibit matrix-degrading function. Furthermore, we found that gelsolin is not required for TLR4-induced podosome disassembly. Thus, the actin cytoskeleton of podosomes involved in dendritic cell extracellular matrix degradation appears to be regulated differently than the cytoskeleton in podosomes of osteoclasts mediating bone resorption.
Highlights
As sentinels of the immune system, dendritic cells (DC) serve as an important link between innate and adaptive immunity
Podosomes exist in a wide array of different cell types, and are involved in distinct processes such degradation of extracellular matrix, bone degradation mediated by osteclasts [8,28], and lymphocyte trans-cellular migration [9]
Gelsolin is a protein frequently mentioned in the literature as one of the key proteins involved in podosome dynamics and function [12,20,21,22,23,24]
Summary
As sentinels of the immune system, dendritic cells (DC) serve as an important link between innate and adaptive immunity. Immature DC reside in peripheral tissues where they detect invading pathogens using receptors, binding to pathogen molecules, such as the toll-like receptor (TLR) family. Tissue DC undergo a process of maturation that is induced, either spontaneously, or following activation by pathogen recognition. Maturation changes the phenotype of the DC, enabling them to migrate to draining lymph nodes [1]. By presenting acquired antigens to T cells in the lymph-node they may either induce an adaptive immune response under inflammatory conditions, or induce tolerance under steady state conditions [2].
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