Seminar

Regulation of adhesion and migration by the Wiskott Aldrich syndrome protein (WASP) in leukocytes and haematological malignancies.

Dr. Yolanda Calle

The Wiskott Aldrich Syndrome Protein WASP is expressed in haematopoietic cells and belongs to the N-WASP/WAVE family of adaptor proteins that mediate de novo actin polymerisation. Mutations in the gene coding for WASP leads to the Wiskott-Aldrich Syndrome WAS, a haematological disorder characterized by eczema, microthrombocytopenia, and immunodeficiency. WASP-deficient leukocytes exhibit defects in the organization and regulation of the actin cytoskeleton including the lack of actin-containing adhesions termed podosomes. These cytoskeletal abnormalities contribute to the observed defects in cell migration and chemotaxis in vitro and in vivo which are thought to underlie the immune dysfunction seen in WAS patients. We will discuss the role of WASP and WIP WASP interacting protein in adhesion and cytoskeletal remodelling in dendritic cells and osteoclasts as well as in haematological malignancies. We propose podosomes play a key role in the tumour microenvironment in multiple myeloma and other haematological tumours.