WASP confers selective advantage for specific hematopoietic cell populations and serves a unique role in marginal zone B-cell homeostasis and function

Westerberg, Lisa S.; Fuente, Miguel A. de la; Wermeling, Fredrik; Ochs, Hans D.; Karlsson, Mikael C. I.; Snapper, Scott B.; Notarangelo, Luigi D.

doi:10.1182/blood-2008-02-140715

Cited by 93 publications

(146 citation statements)

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“…1I). Previous studies have defined defects of peripheral B cell homeostasis in WASp-null mice, with marked deficiency of marginal zone (MZ) cells in particular (6,20,21). No abnormalities of B cell development were detected in bone marrow of all strains.…”

Section: Abnormalities Of Cell Numbers and Proliferativementioning

confidence: 98%

Phosphorylation of WASp is a key regulator of activity and stability in vivo

Blundell

Bouma

Metelo

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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The Wiskott-Aldrich syndrome protein (WASp) is a key cytoskeletal regulator in hematopoietic cells. Covalent modification of a conserved tyrosine by phosphorylation has emerged as an important potential determinant of activity, although the physiological significance remains uncertain. In a murine knockin model, mutation resulting in inability to phosphorylate Y293 (Y293F) mimicked many features of complete WASp-deficiency. Although a phosphomimicking mutant Y293E conferred enhanced actin-polymerization, the cellular phenotype was similar due to functional dysregulation. Furthermore, steady-state levels of Y293E-WASp were markedly reduced compared to wild-type WASp and Y293F-WASp, although partially recoverable by treatment of cells with proteasome inhibitors. Consequently, tyrosine phosphorylation plays a critical role in normal activation of WASp in vivo, and is indispensible for multiple tasks including proliferation, phagocytosis, chemotaxis, and assembly of adhesion structures. Furthermore, it may target WASp for proteasome-mediated degradation, thereby providing a default mechanism for self-limiting stimulation of the Arp2/3 complex. actin polymerization ͉ immune deficiency ͉ Wiskott-Aldrich syndrome

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Section: Abnormalities Of Cell Numbers and Proliferativementioning

confidence: 98%

Phosphorylation of WASp is a key regulator of activity and stability in vivo

Blundell

Bouma

Metelo

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…Antibody class switching and secretion were assessed as previously described using intracellular staining and ELISA for IgG2b and IgG1 (Westerberg et al, 2005(Westerberg et al, , 2008. The frequency of apoptosis was determined as previously described (Cotta-de-Almeida et al, 2007;Westerberg et al, 2008) and apoptotic cells were defined as annexin V high 7AAD lo by flow cytometry.…”

Section: Br Ief Definitive Repor Tmentioning

confidence: 99%

“…In vitro migration of B and T cells and spreading of B and T cells was assessed as previously described (Westerberg et al, 2001(Westerberg et al, , 2008Cotta-de-Almeida et al, 2007). For spreading, T cells were incubated on…”

Section: F-actin Polymerization Assay and Vaccinia Infectionmentioning

confidence: 99%

Activating WASP mutations associated with X-linked neutropenia result in enhanced actin polymerization, altered cytoskeletal responses, and genomic instability in lymphocytes

Westerberg¹,

Meelu²,

Baptista³

et al. 2010

J Cell Biol

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“…WAS-associated immunodeficiency has been traced to mutations of the WASp gene in hematopoietic cells and confirmed in studies using WASp knock-out animals. Defective migration and phagocytosis have been observed in WASp-null neutrophils (18) and macrophages (19), and the directed migration of B-lymphocytes is also WASp-dependent (20). In T-lymphocytes, the formation of critical cell/cell contact points known as immune synapses is contingent on WASp-mediated actin polymeriza-* This work was supported, in whole or in part, by National Institutes of Health tion (21) as is cell polarization and cytokine secretion (22).…”

mentioning

confidence: 99%

Wiskott-Aldrich Syndrome Protein (WASp) Controls the Delivery of Platelet Transforming Growth Factor-β1

Kim

Falet

Hoffmeister

et al. 2013

Journal of Biological Chemistry

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Background:The mechanisms that regulate cytokine secretion from platelets are undefined. Results: Inhibiting the expression or function of the Wiskott-Aldrich syndrome protein (WASp) increases TGF-␤1 release from platelets. Conclusion: WASp curtails the secretion of TGF-␤1 from human and mouse platelets. Significance: Identifying the biochemical mechanisms of cytokine secretion will improve our understanding of platelets vis-à-vis the host immune response.

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WASP confers selective advantage for specific hematopoietic cell populations and serves a unique role in marginal zone B-cell homeostasis and function

Cited by 93 publications

References 50 publications

Phosphorylation of WASp is a key regulator of activity and stability in vivo

Phosphorylation of WASp is a key regulator of activity and stability in vivo

Activating WASP mutations associated with X-linked neutropenia result in enhanced actin polymerization, altered cytoskeletal responses, and genomic instability in lymphocytes

Wiskott-Aldrich Syndrome Protein (WASp) Controls the Delivery of Platelet Transforming Growth Factor-β1

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