Wiskott-Aldrich syndrome: a disorder of haematopoietic cytoskeletal regulation.

The Wiskott-Aldrich Syndrome (WAS) is a rare inherited X-linked recessive disease characterised by immune dysregulation and microthrombocytopenia. Recently, the biological mechanisms that are responsible for the pathophysiology of WAS have been shown to be linked to the regulation of the actin cytoskeleton in haematopoietic cells. The WAS protein (WASp) is now known to be a member of a unique family that share similar domain structures, and that are responsible for transduction of signals from the cell membrane to the actin cytoskeleton. The interactions between WASp, the Rho family GTPase Cdc42, and the cytoskeletal organising complex Arp2/3 are probably critical to many of these functions, which, when disturbed, translate into measurable defects of cell polarisation and motility.

Thrasher AJ ，Burns S 《MICROSCOPY RESEARCH AND TECHNIQUE》

WASp in immune-system organization and function.

Thrasher AJ 《NATURE REVIEWS IMMUNOLOGY》

Wiskott-Aldrich syndrome protein and the cytoskeletal dynamics of dendritic cells.

The regulated migration and spatial localization of dendritic cells in response to environmental signals are critical events during the initiation of physiological immune responses and maintenance of tolerance. Cells deficient in the Wiskott-Aldrich syndrome protein (WASP) have been used to demonstrate the importance of the dynamic remodelling of the actin-based cytoskeleton during the selective adhesion and migration of these cells. Unlike most cell types, macrophages, dendritic cells, and osteoclasts utilize a specialized adhesive array termed the podosome in order to migrate. Podosomes are composed of many of the same structural and regulatory proteins as seen in the more commonly found focal adhesion, but are unique in their requirement for WASP. Without WASP, podosomes cannot form and the affected cells are obliged to use focal adhesions for their migratory activities. Once activated by a series of upstream regulatory proteins, WASP acts as a scaffold for the binding of the potent actin nucleating protein complex known as Arp2/3. This article reviews the available evidence that suggests that failures in the regulation of the actin cytoskeleton may contribute significantly to the immunopathology of the Wiskott-Aldrich syndrome.

Calle Y ，Chou HC ，Thrasher AJ ，Jones GE ... -  《-》

Wiskott-Aldrich syndrome (role of WASP).

Nonoyama S 《-》

Interaction of WASP/Scar proteins with actin and vertebrate Arp2/3 complex.

Marchand JB ，Kaiser DA ，Pollard TD ，Higgs HN ... -  《NATURE CELL BIOLOGY》