Format

Send to

Choose Destination
J Cell Sci. 2016 Jan 15;129(2):298-313. doi: 10.1242/jcs.177691. Epub 2015 Nov 30.

The formins FHOD1 and INF2 regulate inter- and intra-structural contractility of podosomes.

Author information

1
Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Eppendorf, Martinistraße 52, Hamburg 20246, Germany.
2
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 26-28, Nijmegen 6525 GA, The Netherlands.
3
Erasmus University, Wytemaweg 80, Rotterdam 3015 CN, The Netherlands.
4
Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Eppendorf, Martinistraße 52, Hamburg 20246, Germany s.linder@uke.de.

Abstract

Podosomes are actin-rich adhesion structures that depend on Arp2/3-complex-based actin nucleation. We now report the identification of the formins FHOD1 and INF2 as novel components and additional actin-based regulators of podosomes in primary human macrophages. FHOD1 surrounds the podosome core and is also present at podosome-connecting cables, whereas INF2 localizes at the podosome cap structure. Using a variety of microscopy-based methods; including a semiautomated podosome reformation assay, measurement of podosome oscillations, FRAP analysis of single podosomes, and structured illumination microscopy, both formins were found to regulate different aspects of podosome-associated contractility, with FHOD1 mediating actomyosin contractility between podosomes, and INF2 regulating contractile events at individual podosomes. Moreover, INF2 was found to be a crucial regulator of podosome de novo formation and size. Collectively, we identify FHOD1 and INF2 as novel regulators of inter- and intra-structural contractility of podosomes. Podosomes thus present as one of the few currently identified structures which depend on the concerted activity of both Arp2/3 complex and specific formins and might serve as a model system for the analysis of complex actin architectures in cells.

KEYWORDS:

FHOD1; Formins; INF2; Macrophages; Podosomes

PMID:
26621033
DOI:
10.1242/jcs.177691
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center