REVIEW
Podosomes as smart regulators of cellular adhesion

https://doi.org/10.1016/j.ejcb.2005.08.005Get rights and content

Abstract

Podosomes are punctate adhesion structures first described in osteoclasts and next found in src-transformed cells of mesenchymal origin. Podosomes were never observed in cultured epithelial cells where cell–matrix adhesion structures were represented only by focal contacts and hemidesmosomes interacting with microfilaments and intermediate filaments, respectively. Rat bladder carcinoma cells and normal human keratinocytes showed that hemidesmosome-like structures are organized around a core of actin filaments that appears early during cell adhesion and looks similar to those of podosomes described in cells of mesenchymal origin. The epithelial podosome-like structures specifically contain Arp2/3 complex, cortactin, dynamin, gelsolin, N-WASP, VASP, Grb2 and src-like kinase(s). The integrin α3β1 is localized circularly around F-actin cores and co-distributes with paxillin, vinculin and zyxin. The maintenance of the F-actin core and the surrounding hemidesmosomes depends on actin polymerization, src family kinases and Grb2, but not on microtubular integrity. Thus, podosomes are not unique to cells of mesenchymal origin, but also appear in epithelial cells where they may take part in regulating basement membrane adhesion.

Introduction

Since their early description (Zallone et al., 1983; Marchisio et al., 1984) as cell–matrix adhesion structures podosomes were only found in mesenchymal cells and were particularly abundant in hematopoietic stem cell-derived lineages including osteoclasts and some human leukemias (Marchisio et al., 1984, Marchisio et al., 1988; Gaidano et al., 1990). Podosomes were also abundantly assembled in several cell types transformed by src (Marchisio et al., 1984) where they could cluster in complex rosette-like structures (Fig. 1). Indeed, the podosome denomination was chosen to indicate that these adhesion structures were presumably involved in the regulation of cell locomotion (Tarone et al., 1985). Fine electron microscopic analysis showed that individual podosomes corresponded to columnar arrays of actin filaments surrounding a narrow tubular invagination of the plasmalemma roughly perpendicular to the substratum (Nitsch et al., 1989) that may convey membrane-bound or secreted molecules onto the extracellular matrix as also suggested by independent studies (Chen, 1989). Podosomes have cytoskeletal components similar to those found in focal contacts but also contain some unique markers, such as the actin-binding proteins gelsolin, dynamin, and cortactin. Moreover, they are much more dynamic and their assembly takes place also when protein synthesis is temporarily blocked.

Section snippets

Epithelial podosomes as hemidesmosome-organizing centers

Our studies (Spinardi et al., 2004) showed a new podosome-like structure in adhering epithelial cells. Each podosome structure appears to be surrounded by a rosette of hemidesmosomes that suggests an organized unit of cytoskeletal structures related to the firm epithelial adhesion to the basement membrane (Fig. 2). The epithelial podosome-like structures are remarkably similar to those described in several cells types of mesenchymal origin. Both structures are organized around a small tubular

References (13)

There are more references available in the full text version of this article.

Cited by (63)

  • L-plastin phosphorylation regulates the early phase of sealing ring formation by actin bundling process in mouse osteoclasts

    2018, Experimental Cell Research
    Citation Excerpt :

    LPL was shown to make a complex with cortactin [1] and integrin beta (β1 & β3) subunits [33] and regulates actin dynamics in carcinoma cells. Cortactin associates with integrins [55,56,63], and also found in the sealing rings of osteoclasts in a time-dependent manner [12,40]. Although ABDs of LPL has no phosphorylation sites, it can bind to the cytoplasmic domain of integrin β-subunit and make a complex with cortactin [33].

  • Prolactin-Induced Protein regulates cell adhesion in breast cancer

    2015, Biochemical and Biophysical Research Communications
  • Podosomes in muscle cells and their role in the remodeling of neuromuscular postsynaptic machinery

    2014, European Journal of Cell Biology
    Citation Excerpt :

    In some cells, these shapes may span up to 50 μm. Podosomes are usually formed at the ventral surface of cultured cells where the plasma membrane is in contact with the substratum, and one of their functions is to promote cellular adhesion (Linder et al., 2011; Murphy and Courtneidge, 2011; Spinardi and Marchisio, 2006). At the same time, the local exocytosis of proteases allows podosomes to remodel or degrade the extracellular matrix (ECM) to facilitate cellular migration and invasion through tissue and influence intercellular interactions (Linder et al., 2011; Murphy and Courtneidge, 2011).

View all citing articles on Scopus
1

Present address: ConStem, Department of Biotechnology and Biosciences, University of Milano Bicocca, Piazza della Scienza 2, I-20126 Milano, Italy.

View full text