The Role of SWAP-70 in Mast Cell Adhesion

(Project Leader: Prof. Dr. Rolf Jessberger)

Abstract:

Physical interactions of mast cells with other hematopoietic, non-hematopoietic cells, or the extracellular matrix (ECM) are critical to mast cell function, for mast cells reside in a large variety of tissues, often at sites exposed to the environment.  To function in the innate and the adaptive immune system, cell-cell and ECM adhesion contacts of mast cells must be very specifically regulated. Like many other cell types, mast cells need to properly interact with each other (homotypically) and with other cell types (heterotypically) to perform their correct function at the right location and time. Yet, the mechanisms that govern mast cell migration, adhesion and homing are not yet sufficiently understood. SWAP-70 (Fig. 1), a F-actin and PIP3 binding, RhoGTPase interacting protein, which we showed to act in F-actin cytoskeletal rearrangements, cell migration and integrin-mediated adhesion, emerges as an important regulator of mast cell adhesion.

Fig. 1 (click to enlarge)

SWAP-70 functions in c-kit and FcεRI dependent pathways crucial for mast cell activation and adhesion. The proposed project aims at elucidating the role of SWAP-70 in governing mast cell adhesion. Initial evidence shows that SWAP-70 regulates integrin-mediated adhesion, for example to fibronectin. The mechanisms with which SWAP-70 controls mast cell adhesion are unknown. Nothing has been reported on whether other, integrin-independent modes of adhesion are regulated by SWAP-70, and if so, whether a shared general function of SWAP-70 accounts for all these different controls. Besides the mechanisms, the biological consequences of deficient SWAP-70 control of adhesion are unclear. The proposed project aims at answering these questions and thus strives to contribute significantly to our understanding of mast cell biology.

Team:

Prof. Dr. rer. nat. Rolf Jessberger
Dr. Tatsiana Ripich
MSc Carlos Andre Chacon-Martinez
Nadine Kiessling

Contact:

Prof. Dr. Rolf Jessberger
Director, Institute of Physiological Chemistry
Faculty of Medicine Carl Gustav Carus
Dresden University of Technology
Fiedlerstr. 42, MTZ
D-01307 Dresden
Germany

Ph: +49-351-458 6446
Fax: +49-351-458 6305
rolf.jessberger(at)mailbox.tu-dresden.de
http://tu-dresden.de/med/phc/

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