Press Page Reinhard Fässler

A Switchblade-like Signaling Machine for Cells

Integrins are anchor proteins that span the plasma membrane and couple the surrounding with the actin cytoskeleton. Integrins play fundamental roles in numerous important processes including cell migration, cell division and blood clotting. Reinhard Fässler and his team study how integrins execute these diverse functions and how malfunctioning integrins affect organogenesis and disease.

Hair follicles in the mouse tail skin: cell nuclei of the epidermis (blue) and three hair follicles with sebaceous glands. Integrins (red) and a focal adhesion protein (green) are essential for their development.

Integrins are expressed on all mammalian cells. These transmembrane proteins mediate cell adhesion to the extracellular matrix and thereby connect cells with the surrounding environment. Integrins control a variety of cellular functions including cell survival, shape and polarity, cell proliferation and blood clotting. They also coordinate cell migration, which is important for cancer metastasis, wound healing and inflammation: At the cell front, activated integrins fix the cell to the extracellular matrix. At the cell rear, integrins become inactivated enabling cell detachment from extracellular matrix proteins; this allows rear contraction and the cell to be propelled forward.

Role of adhesion during embryonic and postnatal development

In order to decode the multifaceted functions and effects of integrins, the scientists in Reinhard Fässler’s department inactivate integrin genes in mice. The consequence of this intervention in the germline of mice is that either none or functionally impaired integrins are expressed during development. Depending on the tissue type and the age of the mouse, these modifications can cause a vast variety of phenotypes.

Dysfunctions of integrins give rise to disease

In a severe hereditary disease, called Leukocyte Adhesion Deficiency (LAD) type III, immune cells can no longer extravasate from the blood circulation into tissues and platelets cannot clot, thus leading to severe bleeding. Fässler’s team was able to show that patients who suffer from this disease lack a protein necessary to activate integrins on white blood cells and platelets. Given that defective integrins almost always lead to diseases, the results from Fässler’s team may help to develop new drugs in the future.


News

Peter Krenn from the Department Molecular Medicine (Director Reinhard Fässler) at the Max Planck Institute of Biochemistry has found a new way to attack leukemic stem cells. more

Tissue are composed of cells and their surrounding extracellular matrix. During embryonic development, wound healing and cancer metastasis, cells move within tissues. How they do it, is a highly… more

White blood cells (leukocytes) are constantly streaming through our vasculature, searching for pathogens – however, in order to trigger an immune response they need to leave the vessels and migrate… more

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