Macrophage Mesenchymal Migration Requires Podosome Stabilization by Filamin A

Guiet, Romain; Vérollet, Christel; Lamsoul, Isabelle; Cougoule, Céline; Poincloux, Renaud; Labrousse, Arnaud; Calderwood, David A.; Glogauer, Michael; Lutz, Pierre G.; Maridonneau‐Parini, Isabelle

doi:10.1074/jbc.m111.307124

Cited by 75 publications

(78 citation statements)

References 54 publications

(107 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…FilaminA was also concentrated in the cortex region surrounding the actin-rich core (Fig. 3D), as reported by Guiet et al (Guiet et al, 2012). In contrast, Amotl2 was concentrated in actin-rich cores (Fig.…”

Section: Association Of Ll5b and Its Binding Partners With Postsynaptsupporting

confidence: 52%

“…Detection of LL5b in the core domain of exuberant podosomes formed in Amotl2-depleted myotubes supports this possibility. Both Asef2 and Filamin A as well as Amotl2 proteins are known to be associated with and organize actin cytoskeleton (Guiet et al, 2012;Huang et al, 2007;Takabayashi et al, 2010) and we previously reported that low levels of actin are present in the cortex of synaptic podosomes (Proszynski et al, 2009). Alternatively, Asef2 and Filamin A may interact indirectly, with intermediary proteins accounting for the lack of co-localization.…”

Section: Amotl2 Regulates Podosomes and Achrs 2231mentioning

confidence: 99%

“…Amotl2, Asef2, Flii and Filamin A exhibit different localization to domains in different cell types. For instance, Filamin A is located to the core in cultured myotubes and Src3T3 cells but in the cortex in RAW macrophages (Figs 2-4) (Guiet et al, 2012).…”

Section: Amotl2 Regulates Podosomes and Achrs 2231mentioning

confidence: 99%

See 2 more Smart Citations

Amotl2 interacts with LL5β, localizes to podosomes and regulates postsynaptic differentiation in muscle

Prószyński

Sanes²

2013

Journal of Cell Science

View full text Add to dashboard Cite

SummaryNeuromuscular junctions (NMJs) in mammalian skeletal muscle undergo a postnatal topological transformation from a simple oval plaque to a complex branched structure. We previously showed that podosomes, actin-rich adhesive organelles, promote the remodeling process, and demonstrated a key role for one podosome component, LL5b. To further investigate molecular mechanisms of postsynaptic maturation, we purified LL5b-associated proteins from myotubes and showed that three regulators of the actin cytoskeleton -Amotl2, Asef2 and Flii -interact with LL5b. These and other LL5b-interacting proteins are associated with conventional podosomes in macrophages and podosome-like invadopodia in fibroblasts, strengthening the close relationship between synaptic and non-synaptic podosomes. We then focused on Amotl2, showing that it is associated with synaptic podosomes in cultured myotubes and with NMJs in vivo. Depletion of Amotl2 in myotubes leads to increased size of synaptic podosomes and corresponding alterations in postsynaptic topology. Depletion of Amotl2 from fibroblasts disrupts invadopodia in these cells. These results demonstrate a role for Amotl2 in synaptic maturation and support the involvement of podosomes in this process.

show abstract

Section: Association Of Ll5b and Its Binding Partners With Postsynaptsupporting

confidence: 52%

Section: Amotl2 Regulates Podosomes and Achrs 2231mentioning

confidence: 99%

See 1 more Smart Citation

Amotl2 interacts with LL5β, localizes to podosomes and regulates postsynaptic differentiation in muscle

Prószyński

Sanes²

2013

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…Thus, while we did not observe alterations in the levels of secreted MMP9 or MMP2 in HT1080 cells, loss of filamin expression is now associated with increased activation or expression of MMPs in several cell types. Conversely, in macrophages FLNa localizes to and stabilizes podosomes thus enhancing ECM degradation (Guiet et al, 2012), indicating that the effect of filamin on matrix degradation is cell type specific.…”

Section: Discussionmentioning

confidence: 99%

Filamin A controls matrix metalloprotease activity and regulates cell invasion in human fibrosarcoma cells.

Baldassarre

Razinia

Brahme

et al. 2012

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

SummaryFilamins are an important family of actin-binding proteins that, in addition to bundling actin filaments, link cell surface adhesion proteins, signaling receptors and channels to the actin cytoskeleton, and serve as scaffolds for an array of intracellular signaling proteins. Filamins are known to regulate the actin cytoskeleton, act as mechanosensors that modulate tissue responses to matrix density, control cell motility and inhibit activation of integrin adhesion receptors. In this study, we extend the repertoire of filamin activities to include control of extracellular matrix (ECM) degradation. We show that knockdown of filamin increases matrix metalloproteinase (MMP) activity and induces MMP2 activation, enhancing the ability of cells to remodel the ECM and increasing their invasive potential, without significantly altering two-dimensional random cell migration. We further show that within filamin A, the actin-binding domain is necessary, but not sufficient, to suppress the ECM degradation seen in filamin-A-knockdown cells and that dimerization and integrin binding are not required. Filamin mutations are associated with neuronal migration disorders and a range of congenital malformations characterized by skeletal dysplasia and various combinations of cardiac, craniofacial and intestinal anomalies. Furthermore, in breast cancers loss of filamin A has been correlated with increased metastatic potential. Our data suggest that effects on ECM remodeling and cell invasion should be considered when attempting to provide cellular explanations for the physiological and pathological effects of altered filamin expression or filamin mutations.

show abstract

“…Previous studies showed that filopodia are sensors of chemotaxis. The filopodia projection detects changes in the environment and controls the direction of cell migration (Arjonen et al, 2011;Guiet et al, 2012). However, few studies have been published concerning the role of filopodia in OC differentiation and fusion.…”

Section: Introductionmentioning

confidence: 99%

New roles of filopodia and podosomes in the differentiation and fusion process of osteoclasts

et al. 2014

View full text Add to dashboard Cite

ABSTRACT. The cytoskeleton mediates various cellular processes such as differentiation and fusion, including in the filopodia and podosomes. However, apart from cell migration and formation of the sealing zone, little is known regarding the changes and related regulatory mechanisms of the cytoskeleton and additional roles of the filopodia and podosomes during the differentiation and fusion of osteoclasts. The cytomorphology and cytoskeleton of osteoclasts in the differentiation process were evaluated using tartrate-resistant acid phosphatase staining and immunofluorescence staining. Moreover, the expression levels of Rho GTPases and enzymes related to osteoclast differentiation and bone resorption were detected by quantitative reverse transcription-polymerase chain reaction. We detected 3 types of filopodia in osteoclast precursors and only 1 type of filopodia in undifferentiated cells. Mature osteoclasts were completely devoid of filopodia. Interestingly, cell fusion was highly specific, and the fusion New roles of filopodia and podosomes of osteoclasts initially occurred to the filopodia. Confocal images revealed that F-actin and microtubules significantly differed among fused cells. These results suggest that filopodia and podosomes not only play important roles in cell migration and the formation of sealing zones but also in the prefusion selectivity of 2 cells and the movement direction of the cell nucleus and cytoplasm during the fusion process. In addition, cdc42v1, RhoU, and RhoF regulate the formation of 3 types of filopodia during various stages of differentiation, while Rac1, Rac2, and filament A may be associated with cell selectivity during the fusion process.

show abstract

Macrophage Mesenchymal Migration Requires Podosome Stabilization by Filamin A

Cited by 75 publications

References 54 publications

Amotl2 interacts with LL5β, localizes to podosomes and regulates postsynaptic differentiation in muscle

Amotl2 interacts with LL5β, localizes to podosomes and regulates postsynaptic differentiation in muscle

Filamin A controls matrix metalloprotease activity and regulates cell invasion in human fibrosarcoma cells.

New roles of filopodia and podosomes in the differentiation and fusion process of osteoclasts

Contact Info

Product

Resources

About