Cell adhesion and intracellular transport

Group leader: Coert Margadant PhD

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Integrins are cell-surface receptors that regulate signaling, cell adhesion, and cell migration, which lie at the basis of many physiological and pathological processes including immune surveillance, blood clotting, and wound healing. Integrins are therefore essential for human health, and the deregulation of integrin function can cause a variety of diseases such as bleeding disorders, leukocyte adhesion deficiencies, blistering diseases and cancer.
We study the mechanisms that control integrin function, and the transduction of integrin signals into cellular responses. Furthermore, we investigate how the cellular transport machinery regulates the delivery and turnover of integrins, to coordinate the dynamic regulation of adhesion and migration.

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Ongoing research

Integrins adopt conformations with different affinities for ligand, and the allosteric change that favors the high-affinity conformation is called integrin activation. Integrin activation is regulated by signaling pathways and involves a number of proteins that bind directly to integrin cytoplasmic tails. Downstream of ligand-binding, integrins assemble large multimeric protein complexes (containing up to 250 different proteins) that connect to the cytoskeleton and regulate cell adhesion, signaling and motility. Furthermore, integrins traffic through the cell in vesicular compartments, where they are sorted for degradation or recycling by components of the cellular transport machinery. These events ensure integrin cell-surface expression, turnover, and redistribution to specific sites in the cell, and are particularly important in migrating cells.
The main focus of our research is to unravel how the components of these complexes and compartments regulate integrin function or integrin-stimulated processes, and to identify novel integrin regulators and integrin-associated proteins. We use a combination of approaches in a variety of cellular model systems, including gene deletion and reconstitution, shRNA-mediated gene silencing, and mass spectrometry. Effects on integrin function and integrin-dependent processes are investigated using cell-biological techniques including flow cytometry and confocal microscopy.

Motivated undergraduate students are welcome to participate in the ongoing research of the group. Research projects will typically include a variety of (molecular) cell biology techniques (cloning, tissue culture, flow cytometry, Western blotting, confocal and time-lapse microscopy, transfections, viral transductions etc.), depending on interests and experience.

If you are interested please contact Coert Margadant: c.margadant@sanquin.nl

Last edited on: 25 March 2015