Spatiotemporal regulation of Src and its substrates at invadosomes

Boateng, Lindsy R.; Huttenlocher, Anna

doi:10.1016/j.ejcb.2012.06.003

Cited by 40 publications

(41 citation statements)

References 184 publications

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“…As some of the invadosome components are common to the different types of invadosomes that have been described, the existence of a common precursor has been suggested (Boateng and Huttenlocher, 2012;Gimona et al, 2008;Linder, 2009;Linder et al, 2011). Here, we wish to raise the possibility that, in reality, this apparent variability in fact represents the ability of a common invadosome precursor to adapt to its microenvironment, for example to modulate its morphology according to the substrate it encounters, such as taking on a linear shape along a type I collagen fibril.…”

Section: Invadosome Plasticitymentioning

confidence: 99%

The microenvironment controls invadosome plasticity

Martino

Henriet

Ezzoukhry

et al. 2016

Journal of Cell Science

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Invadosomes are actin-based structures involved in extracellular matrix degradation. Invadosomes is a term that includes podosomes and invadopodia, which decorate normal and tumour cells, respectively. They are mainly organised into dots or rosettes, and podosomes and invadopodia are often compared and contrasted. Various internal or external stimuli have been shown to induce their formation and/or activity. In this Commentary, we address the impact of the microenvironment and the role of matrix receptors on the formation, and dynamic and degradative activities of invadosomes. In particular, we highlight recent findings regarding the role of type I collagen fibrils in inducing the formation of a new linear organisation of invadosomes. We will also discuss invadosome plasticity more generally and emphasise its physio-pathological relevance.

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Section: Invadosome Plasticitymentioning

confidence: 99%

The microenvironment controls invadosome plasticity

Martino

Henriet

Ezzoukhry

et al. 2016

Journal of Cell Science

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“…Invadosomes are actin-rich adhesion structures containing a dense meshwork of actin filaments at their center, or core, and a ring of adhesion adapter proteins, such as paxillin and vinculin, at their periphery [13,14]. Invadopodia play an important role in tumor cell invasion, representing the site of intense matrix degradation by tumor cells [15–17].…”

Section: Introductionmentioning

confidence: 99%

Myosin 1e is a component of the invadosome core that contributes to regulation of invadosome dynamics

Ouderkirk

Krendel

2014

Experimental Cell Research

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Myosin 1e (myo1e) is an actin-based motor protein that has been implicated in cell adhesion and migration. We examined the role of myo1e in invadosomes, actin-rich adhesion structures that are important for degradation and invasion of the extracellular matrix. RSV-transformed BHK-21 cells, which readily form invadosomes and invadosome rosettes, were used as the experimental model. Myo1e localization to the actin-rich core of invadosomes required the proline-rich Tail Homology 2 (TH2) domain. During invadosome rosette expansion, we observed myo1e recruitment to newly forming invadosomes via Tail Homology 1 (TH1)-dependent interactions with the plasma membrane, where it preceded actin and paxillin. Dominant-negative inhibition of myo1e resulted in mislocalized invadosome formation, usually at the center of the rosette. We propose that TH2 domain of myo1e provides the key signal for localization to invadosomes, while TH1 domain interactions facilitate myo1e targeting to the plasma membrane-proximal locations within the rosettes. Myo1e may then act as a scaffold, linking the plasma membrane with the actin cytoskeleton and helping direct new invadosome formation to the periphery of the rosette.

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“…Active Src regulates invadosome formation in non-neuronal cells through phosphorylation of both Tks5 and Cttn (Boateng and Huttenlocher, 2012). As active Src targets to growth cone invadosomes, we tested Src inhibitors on growth cone invadosome formation.…”

Section: Both the Inhibition Of Src And The Disruption Of Lipid Raftsmentioning

confidence: 99%

Regulation of ECM degradation and axon guidance by growth cone invadosomes

et al. 2015

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Invadopodia and podosomes, collectively referred to as invadosomes, are F-actin-rich basal protrusions of cells that provide sites of attachment to and degradation of the extracellular matrix. Invadosomes promote the invasion of cells, ranging from metastatic cancer cells to immune cells, into tissue. Here, we show that neuronal growth cones form protrusions that share molecular, structural and functional characteristics of invadosomes. Growth cones from all neuron types and species examined, including a variety of human neurons, form invadosomes both in vitro and in vivo. Growth cone invadosomes contain dynamic F-actin and several actin regulatory proteins, as well as Tks5 and matrix metalloproteinases, which locally degrade the matrix. When viewed using three-dimensional superresolution microscopy, F-actin foci often extended together with microtubules within orthogonal protrusions emanating from the growth cone central domain. Finally, inhibiting the function of Tks5 both reduced matrix degradation in vitro and disrupted motoneuron axons from exiting the spinal cord and extending into the periphery. Taken together, our results suggest that growth cones use invadosomes to target protease activity during axon guidance through tissues.

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Spatiotemporal regulation of Src and its substrates at invadosomes

Cited by 40 publications

References 184 publications

The microenvironment controls invadosome plasticity

The microenvironment controls invadosome plasticity

Myosin 1e is a component of the invadosome core that contributes to regulation of invadosome dynamics

Regulation of ECM degradation and axon guidance by growth cone invadosomes

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