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B4: Regulation of hematopoietic cell differentiation, adhesion, migration, and lymphoid tissue formation by the SWEF proteins

Project leader: Prof. Dr. R. Jessberger

Key insights into the role of SWAP-70 in development and features of hematopoietic cell lineages were obtained. SWAP-70 is an unusual F-actin and RhoGTPase binding protein. B cell differentiation, but also erythrocyte progenitor differentiation and hematopoietic stem cell features, were investigated. The data, published in 5 publications of this funding period, and additional results strongly argue for a central hypothesis for SWAP-70's cytoplasmic activity, where SWAP-70 controls cell properties through regulation of specific F-actin rearrangements. Thereby SWAP-70 modulates integrin activity, migration, cell morphogenesis and related processes. Besides its cytoplasmic functions, a nuclear role of SWAP-70 in control of B cell differentiation was identified, and initial results on DEF6, the only protein closely related to SWAP-70, together the "SWEF" proteins, were obtained.

Our aims for the next funding period are: (A) To understand the molecular and cellular role of nuclear SWAP-70 in B cell differentiation; (B) to further define SWAP-70's role in hematopoietic cell adhesion and migration and the underlying F-actin control mechanism; (C) to start determining the functional relationship between SWAP-70 and DEF6 in B cell development. Molecular and cellular approaches and newly completed mouse models will allow us to comprehensively address these questions, and will yield a much better understanding of hematopoietic cell control by SWAP-70 and the SWEF branch.


« January 2020 »

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