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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Cells, Cultured
  • Extracellular Matrix / metabolism
  • Fetal Proteins / physiology*
  • Formins
  • Humans
  • Macrophages / metabolism
  • Macrophages / ultrastructure
  • Microfilament Proteins / physiology*
  • Nuclear Proteins / physiology*
  • Podosomes / physiology*
  • Podosomes / ultrastructure

Substances

  • Actins
  • FHOD1 protein, human
  • Fetal Proteins
  • Formins
  • INF2 protein, human
  • Microfilament Proteins
  • Nuclear Proteins