Top publications on podosomes

Podosomes

Antigen-presenting dendritic cells (DCs) reside in peripheral tissues and patrol for foreign antigens. DCs use actomyosin-based structures called podosomes to explore and remodel the surrounding extracellular matrix. Podosomes have a round actin core surrounded by a ring of integrins and cytoskeletal proteins such as talin, vinculin and paxillin.

Recently, a research team headed by Alessandra Cambi (Department of Tumor Immunology) published two articles in category top journals that significantly further our understanding of podosome function. These publications are the rewarding achievements of two talented PhD students, Marjolein Meddens and Koen van den Dries (currently postdoc at Yale University). In the Microscopy and Microanalysis article, the authors developed a novel quantitative image analysis algorithm for rapid and accurate large-scale analysis of podosomes that allowed them to reveal a differential distribution of cytoskeletal adaptor proteins that seems essential for their mechanosensory function.

In the Nature Communications article, they combined this algorithm with complementary microscopy techniques and revealed how the actomyosin apparatus coordinate the integrity and dynamics of the protrusive core and the adhesive ring. This previously unrecognized actomyosin interplay provides novel mechanistic insights into how DCs sense and respond to the extracellular environment. DCs are exploited for cancer vaccines, and their capacity to reach the lymph nodes to induce an anti-tumor immune response is essential. Podosome dissolution is the first step towards the acquisition of a migratory phenotype, and more insight into DC migratory properties could potentially improve the efficacy of these clinical trials. To note, macrophages, osteoclasts, megakaryocites and endothelial cells also form podosomes, while invading cancer cells form podosome-like structures called invadopodia. Fundamental research on the properties and function of these structures may contribute to understand pathologies such as vascular diseases, impaired bone resorption and tissue invasion by cancer cells.

Meddens MBM, Rieger B, Figdor CG, Cambi A and van den Dries K (2013) "Automated podosome identification and characterization in fluorescence microscopy images" Microsc Microanal DOI: http://dx.doi.org/10.1017/S1431927612014018  Published online: 25 January 2013. http://www.ncbi.nlm.nih.gov/pubmed/23347434

Van den Dries K, Meddens M, de Keijzer S, Shekhar S, Subramaniam V, Figdor CG and Cambi A (2013) "Interplay between myosin IIA-mediated contractility and actin network integrity orchestrates podosome composition and oscillations". Nat. Commun. DOI: 10.1038/ncomms2402, Published online: 29 January 2013. http://www.ncbi.nlm.nih.gov/pubmed/23361003

Meddens en Den Dries Koen van den Dries (left) and Marjolein Meddens (right).

 

 


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