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Tools of the trade: podosomes as multipurpose organelles of monocytic cells

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Abstract

Podosomes are adhesion and invasion structures that are particularly prominent in cells of the monocytic lineage such as macrophages, dendritic cells, and osteoclasts. They are multifunctional organelles that combine several key abilities required for cell migration and invasion. The podosome repertoire includes well-established functions such as cell-substrate adhesion, and extracellular matrix degradation, recently discovered abilities such as rigidity and topology sensing as well as antigen sampling, and also more speculative functions such as cell protrusion stabilization and transmigration. Collectively, podosomes not only enable dynamic interactions of cells with their surroundings, they also gather information about the pericellular environment, and are actively involved in its reshaping. This review presents an overview of the current knowledge on podosome composition, architecture, and regulation. We focus in particular on the growing list of podosome functions and discuss the specific properties of podosomes in macrophages, dendritic cells, and osteoclasts. Moreover, this article highlights podosome-related intracellular transport processes, the formation of podosomes in 3D environments as well as potentially podosome-associated diseases involving monocytic cells.

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Abbreviations

ADAM:

A disintegrin and metalloproteinase

Arp:

Actin-related protein

CD:

Cluster of differentiation

ECM:

Extracellular matrix

FMNL:

Formin-like

HDAC:

Histone deacetylase

KIF:

Kinesin-like

LAD:

Leukocyte adhesion deficiency

MMP:

Matrix metalloproteinase

MT1-MMP:

Membrane-type 1-matrix metalloproteinase

PAPA:

Pyogenic sterile arthritis, pyoderma gangrenosum, and acne (syndrome)

PSTPIP:

Proline-serine-threonine phosphatase interacting protein

PMA:

Phorbol 12-myristate 13-acetate

SZ:

Sealing zone

TAM:

Tumor-associated macrophage

WAS:

Wiskott-Aldrich syndrome

WASP:

Wiskott-Aldrich syndrome protein

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Acknowledgments

We thank Koen van den Dries for contributing images and discussions. We apologize to all authors whose work was not mentioned owing to space limitations. Current research on podosomes in the SL lab has received funding from Deutsche Forschungsgemeinschaft (LI925/2-2, LI925/3-2) and the Wilhelm Sander-Stiftung (2012.026.1).

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Linder, S., Wiesner, C. Tools of the trade: podosomes as multipurpose organelles of monocytic cells. Cell. Mol. Life Sci. 72, 121–135 (2015). https://doi.org/10.1007/s00018-014-1731-z

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  • DOI: https://doi.org/10.1007/s00018-014-1731-z

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