Membrane Receptors in Cell Adhesion

A broad spectrum of biological processes requires controlled cell adhesion, including embryonic development, assembly of tissues and the nervous system, cellular communication, inflammation and wound healing, tumor metastasis, cell culturing, and viral and bacterial infection. Although much is known about cell adhesion, many questions remain unanswered owing to its multiple facets and complexity. Cell adhesion is commonly defined as the binding of a cell to a substrate, which can be another cell, a surface or an organic matrix. The process is regulated by specific cell-adhesion molecules (CAMs), which are typically transmembrane receptors that comprise an intracellular domain that interacts with cytoplasmic proteins, including the cytoskeleton, and an extracellular domain that specifically binds to adhesion partners. Binding is commonly heterotypic, but it can be homotypic, such as that involving cadherins. The major classes of CAMs in mammals include cadherins, selectins, integrins and Ig-CAMs (cell-adhesion molecules of the immunoglobulin superfamily). Molecular and genetic approaches have identified the adhesion proteins and their ligand specificities, and have determined the processes in which they are involved. However, the molecular mechanisms by which CAMs work and how they regulate different types of adhesion are open debates. For example, an extensive array of proteins is known to be involved in adhesive assemblies, i.e. focal adhesions [cell–extracellular-matrix (ECM) junctions], but the contributions of these proteins to the strength of adhesion are not quantitatively understood. To understand cell adhesion, therefore, the vast amount of qualitative data that is available must be augmented with quantitative data of the physics of adhesion. Here we combine single-cell force spectroscopy (SCFS) with other microscopies and with cell biologicaland genetic tools to characterize how cells initiate and strengthen adhesion.

Teneurins are evolutionarily conserved transmembrane receptors that function as axon guidance and target selection molecules in the developing nervous system. How teneurins recognize each other, whether they establish neuronal adhesion, and which teneurin specific interactions guide neurons remained to be determined. To reveal insight into these pertinent questions we combined atomic force microscopy-based single-cell force spectroscopy with genetic engineering and quantify the interactions teneurins establish between animal cells. Shown is the result of these experiments a model of how the individual teneurin domains contribute to select and strengthen homophilic cell−cell adhesion. Interaction between the NHL domains controls homophilic recognition between teneurins. Strengthening of homophilic cell adhesion requires the presence of the intracellular domains, which are supposed to connect teneurins to the actin cytoskeleton. Figure adapted from J. Beckmann et al. Nano Letters (2013) 13, 2937-2946.
Teneurins are evolutionarily conserved transmembrane receptors that function as axon guidance and target selection molecules in the developing nervous system. How teneurins recognize each other, whether they establish neuronal adhesion, and which teneurin specific interactions guide neurons remained to be determined. To reveal insight into these pertinent questions we combined SCFS with genetic engineering and quantify the interactions teneurins establish between animal cells. Shown is the result of these experiments a model of how the individual teneurin domains contribute to select and strengthen homophilic cell−cell adhesion. Interaction between the NHL domains controls homophilic recognition between teneurins. Strengthening of homophilic cell adhesion requires the presence of the intracellular domains, which are supposed to connect teneurins to the actin cytoskeleton. Figure adapted from J. Beckmann et al. Nano Letters (2013) 13, 2937-2946.

Further reading

 

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eLife 
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FEBS Letters (2014) 588, 3639-3648.

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PLoS One (2013) 8, e71485.

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Nano Letters (2013) 13, 2937-2946.

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Methods (2013) 60, 169–178.

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Force probing surfaces of living cells to molecular resolution

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New frontiers in atomic force microscopy: Analyzing interactions from single-molecules to cells

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Current Opinion in Biotechnology (2009) 20, 4-13.

TPA primes α2β1 integrins for cell adhesion

M. TullaJ. HeleniusD.J. Müller & J. Heino
FEBS Letters (2008) 582, 3520-3524.

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Quantifying adhesive and tensile cell properties determining germ layer organization during gastrulation

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Science STKE (2007) 406, pl5.

Galectin-3 and galectin-9 contribute to adhesion and cystogenesis in epithelial MDCK cells

J. Friedrichs, J. Torkko, J. Helenius, J. Füllekrug, D.J. Müller, K. Simons & A. Manninen
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Measuring cell adhesion forces of primary gastrulating cells from zebrafish using atomic force microscopy

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