Integrin diversity brings specificity in mechanotransduction

Seetharaman, Shailaja; Etienne-Manneville, Sandrine

doi:10.1111/boc.201700060

Cited by 103 publications

(96 citation statements)

References 136 publications

(178 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We therefore suggest that this behavior may originate from the integrins that are involved in cell adhesion. Integrins subtypes have been shown to differently contribute to rigidity probing (60). For instance traction forces transmitted by α 6 β 1 integrins which are involved in cell adhesion on LN (61) were shown to be of smaller amplitude than those transmitted by the α 5 β 1 integrins on FN (62).…”

Section: Discussionmentioning

confidence: 99%

Glial cell mechanosensitivity is reversed by adhesion cues

Tomba¹,

Migdal²,

Fuard³

et al. 2019

Preprint

View full text Add to dashboard Cite

Brain tissues demonstrate heterogeneous mechanical properties, which evolve with aging and pathologies. The observation in these tissues of smooth to sharp rigidity gradients raises the question of brain cells responses to both different values of rigidity and their spatial variations. Here, we use recent techniques of hydrogel photopolymerization to achieve stiffness structuration down to micrometer resolution. We investigate primary neuron adhesion and orientation as well as glial cell adhesive and proliferative properties on multi-rigidity polyacrylamide hydrogels presenting a uniform density of adhesive molecules. We first observed that neurons grow following rigidity gradients. Then, our main observation is that glial cell adhesion and proliferation can be enhanced on stiff or on soft regions depending on the adhesive coating of the hydrogel, i. e. fibronectin or poly-L-lysine/laminin. This behavior was unchanged in the presence or not of neuronal cells. In addition, and contrarily to other cell types, glial cells were not confined by sharp, micron-scaled gradients of rigidity. Our observations suggest that their mechanosensitivity could involve adheison-related mechanosensitive pathways that are specific to brain tissues. SIGNIFICANCE By growing primary brain cells on 2D multi-rigidity polyacrylamide hydrogels, we show that favorable culture conditions for glial cells switch from stiff to soft substrates when changing the adhesive ligands from fibronectin to poly-L-lysine/laminin. Together with neurons, glial cells thus provide a unique example where soft is preferred to stiff, but unlike neurons, this preference can be reversed by changing the nature of the coating. We additionally show that contrarily to other cell types, glial cells are deformed by subcellular gradients of rigidity but cannot be confined by these rigidity gradients. These observations point that glial cell use a very specific, integrin-related machinery for rigidity sensing.

show abstract

Section: Discussionmentioning

confidence: 99%

Glial cell mechanosensitivity is reversed by adhesion cues

Tomba¹,

Migdal²,

Fuard³

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Thus, multiple protein complexes that appear to be cell type specific and may associate with FAs dependent on distinct integrin subtypes (Seetharaman and Etienne-Manneville, 2018), are not only involved in recruiting microtubules to the vicinity of FAs, but also in keeping them anchored at these sites by preventing their depolymerisation or removal by the actin retrograde flow. In turn, FA-associated microtubules can also contribute to intracellular transport and signalling to alter FA dynamics as discussed below.…”

Section: Recruitment Of Cortical Partners Near Fasmentioning

confidence: 99%

“…α 6 β 4 integrins form the core of hemidesmosomes, which mainly connect to the intermediate filament network (Walko et al, 2015), although some recent reports have suggested that microtubules can also be associated with hemidesmosomes (Quintin et al, 2016). In contrast to hemidesmosomes, FAs and podosomes vary in their integrin composition and are mainly associated with the actin cytoskeleton (Seetharaman and Etienne-Manneville, 2018). FAs and the smaller focal complexes are adhesive structures that are essential for cell spreading and cell motility.…”

Section: Introductionmentioning

confidence: 99%

“…Stress fibres, formed by long actin cables intertwined with myosin, are anchored at FAs through several molecular linkers, including mechanosensing proteins, such as talins or vinculin (Tojkander et al, 2012;Yan et al, 2015). FAs integrate several extracellular cues, including the biochemical nature of the integrin-bound ligand and the physical properties of the substrate, to influence the adaptation of cell behaviour to the microenvironment (Seetharaman and Etienne-Manneville, 2018). In particular, FAs modulate the acto-myosin network, which generates forces for cell contraction, shape changes and migration (De Pascalis and Etienne- .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Microtubules at focal adhesions – a double-edged sword

Seetharaman

Etienne-Manneville

2019

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

Cell adhesion to the extracellular matrix is essential for cellular processes, such as migration and invasion. In response to cues from the microenvironment, integrin-mediated adhesions alter cellular behaviour through cytoskeletal rearrangements. The tight association of the actin cytoskeleton with adhesive structures has been extensively studied, whereas the microtubule network in this context has gathered far less attention. In recent years, however, microtubules have emerged as key regulators of cell adhesion and migration through their participation in adhesion turnover and cellular signalling. In this Review, we focus on the interactions between microtubules and integrin-mediated adhesions, in particular, focal adhesions and podosomes. Starting with the association of microtubules with these adhesive structures, we describe the classical role of microtubules in vesicular trafficking, which is involved in the turnover of cell adhesions, before discussing how microtubules can also influence the actin-focal adhesion interplay through RhoGTPase signalling, thereby orchestrating a very crucial crosstalk between the cytoskeletal networks and adhesions.

show abstract

“…A central element to mechanobiology is the understanding of how cells probe their extracellular environment (neighbouring cells and the ECM components) and exert or feel forces to mediate different cellular responses via adhesive proteins such as integrins, cadherins, and other mechanosensitive receptors [Sluysmans et al., ; Seetharaman and Etienne‐Manneville, ]. However, we want to specify here that the purpose of this editorial is not to describe the signalling processes induced by mechanical stresses, but to focus on how cells experience forces.…”

mentioning

confidence: 99%