Retroviral WASP gene transfer into human hematopoietic stem cells reconstitutes the actin cytoskeleton in myeloid progeny cells differentiated in vitro

Dewey, Ricardo Alfredo; Díez, Inés Avedillo; Ballmaier, Matthias; Filipovich, Alexandra H.; Greil, Johann; Güngör, Tayfun; Happel, Christoph M.; Maschan, Alexey; Noyan, Fatih; Pannicke, Ulrich; Schwarz, Klaus; Snapper, Scott B.; Welte, Karl; Klein, Christoph

doi:10.1016/j.exphem.2006.04.021

Cited by 31 publications

(28 citation statements)

References 29 publications

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“…Current strategies target gene delivery to hematopoietic stem cells potentially to correct all hematopoietic cell lineages. 47,48 In addition, the high incidence of reversion cases in patients with WAS should be taken into consideration during the evaluation of the best therapeutic options, including gene therapy.…”

Section: Discussionmentioning

confidence: 99%

Revertant T lymphocytes in a patient with Wiskott-Aldrich syndrome: Analysis of function and distribution in lymphoid organs

Trifari¹,

Scaramuzza²,

Catucci³

et al. 2010

Journal of Allergy and Clinical Immunology

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Section: Discussionmentioning

confidence: 99%

Revertant T lymphocytes in a patient with Wiskott-Aldrich syndrome: Analysis of function and distribution in lymphoid organs

Trifari¹,

Scaramuzza²,

Catucci³

et al. 2010

Journal of Allergy and Clinical Immunology

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“…Two recent studies show that WASP gene transfer into HPC from WAS patients reconstitutes the actin cytoskeleton in myeloid progeny cells differentiated in vitro. 5,40 Moreover, a modest advantage of WASPexpressing neutrophils and myeloid cells was seen using BM competitive repopulation experiments. 29 However, we found little or no evidence of selective advantage for WASP expressing myeloid cells in WASP ϩ/Ϫ mice and on in vitro culture with M-CSF or GM-CSF.…”

Section: Discussionmentioning

confidence: 99%

“…4 In severe cases, where suitable donors are unavailable, gene therapy is being considered as an alternative treatment for WAS. 5,6 However, the role of WASP in the development of hematopoietic cells remains largely unknown. A detailed analysis of the possible advantage for WASP-expressing cells over WASP-negative cells in a competitive setting should provide insight into which lineages are more probable to be corrected by gene therapy.…”

Section: Introductionmentioning

confidence: 99%

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

Westerberg

Fuente

Wermeling

et al. 2008

Blood

126

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“…However, upon binding of guanosine triphosphate (GTP) loaded-Cdc42 the VCA region is released and the C-terminal region is capable of binding to the Arp2/3 complex, to stimulate actin polymerization (Kim et al, 2000). Fc ␥ R-mediated phagocytosis is impaired in peripheral blood monocytes for Wiskott-Aldrich syndrome patients in which formation of the actin cup is also markedly attenuated (Lorenzi et al, 2000;Dewey et al, 2006). Furthermore, the VCA region of WASP was demonstrated to be critical for the phagocytic cup formation (Tsuboi and Meerloo, 2007).…”

mentioning

confidence: 99%

Cdc42 Regulates Fc_γReceptor-mediated Phagocytosis through the Activation and Phosphorylation of Wiskott-Aldrich Syndrome Protein (WASP) and Neural-WASP

Park¹,

Cox

2009

MBoC

111

100

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Cdc42 is a key regulator of the actin cytoskeleton and activator of Wiskott-Aldrich syndrome protein (WASP).Although several studies have separately demonstrated the requirement for both Cdc42 and WASP in Fc ␥ receptor (Fc ␥ R)-mediated phagocytosis, their precise roles in the signal cascade leading to engulfment are still unclear. Reduction of endogenous Cdc42 expression by using RNA-mediated interference (short hairpin RNA [shRNA]) severely impaired the phagocytic capacity of RAW/LR5 macrophages, due to defects in phagocytic cup formation, actin assembly, and pseudopod extension. Addition of wiskostatin, a WASP/neural-WASP (N-WASP) inhibitor showed extensive inhibition of phagocytosis, actin assembly, and cell extension identical to the phenotype seen upon reduction of Cdc42 expression. However, using WASP-deficient bone marrow-derived macrophages or shRNA of WASP or N-WASP indicated a requirement for both WASP and N-WASP in phagocytosis. Cdc42 was necessary for WASP/N-WASP activation, as determined using a conformation-sensitive antibody against WASP/N-WASP and partial restoration of phagocytosis in Cdc42 reduced cells by expression of a constitutively activated WASP. In addition, Cdc42 was required for proper WASP tyrosine phosphorylation, which was also necessary for phagocytosis. These results indicate that Cdc42 is essential for the activation of WASP and N-WASP, leading to actin assembly and phagocytic cup formation by macrophages during Fc ␥ R-mediated phagocytosis. INTRODUCTIONPhagocytosis, the mechanism of internalization of particles Ͼ0.5 m, is used by specialized cells such as macrophages, dendritic cells, and neutrophils for the clearance of foreign particles and cellular debris (Aderem and Underhill, 1999). This process is initiated by the recognition by diverse phagocytic receptors on the cell surface, including the complement receptor (CR) 3 (or ␣ M ␤ 2 ) and the Fc ␥ receptor (Fc ␥ R), two of the best-characterized phagocytic receptors. Ligation of these receptors initiates a complex series of events, including actin assembly, membrane extension, and fusion, ultimately leading to particle internalization .The Rho family GTPases (Rac, Rho, and Cdc42) regulate numerous cell functions, many requiring alterations of the cytoskeleton, including Fc ␥ R-and complement-mediated phagocytosis (reviewed in Ridley, 2001;Fenteany and Glogauer, 2004). Interestingly, these three GTPases have been shown to differentially regulate the phagocytic process. Phagocytosis mediated by the Fc ␥ R has been shown to require both Rac and Cdc42 (Cox et al., 1997;Massol et al., 1998) but not Rho (Caron and Hall, 1998). By contrast, particle uptake mediated by the CR3 requires Rho but not Rac or Cdc42 (Caron and Hall, 1998). Rac1 and Cdc42 function is required for Fc ␥ R-mediated phagocytic cup formation (Cox et al., 1997). The differential recruitment, localization, and activation of Rac and Cdc42 during Fc ␥ R-mediated phagocytosis suggest a precise and unique function for each Rho GTPase in coordinating this process (Pat...

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Retroviral WASP gene transfer into human hematopoietic stem cells reconstitutes the actin cytoskeleton in myeloid progeny cells differentiated in vitro

Cited by 31 publications

References 29 publications

Revertant T lymphocytes in a patient with Wiskott-Aldrich syndrome: Analysis of function and distribution in lymphoid organs

Revertant T lymphocytes in a patient with Wiskott-Aldrich syndrome: Analysis of function and distribution in lymphoid organs

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

Cdc42 Regulates Fc_γReceptor-mediated Phagocytosis through the Activation and Phosphorylation of Wiskott-Aldrich Syndrome Protein (WASP) and Neural-WASP

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Retroviral WASP gene transfer into human hematopoietic stem cells reconstitutes the actin cytoskeleton in myeloid progeny cells differentiated in vitro

Cited by 31 publications

References 29 publications

Revertant T lymphocytes in a patient with Wiskott-Aldrich syndrome: Analysis of function and distribution in lymphoid organs

Revertant T lymphocytes in a patient with Wiskott-Aldrich syndrome: Analysis of function and distribution in lymphoid organs

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

Cdc42 Regulates FcγReceptor-mediated Phagocytosis through the Activation and Phosphorylation of Wiskott-Aldrich Syndrome Protein (WASP) and Neural-WASP

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About

Cdc42 Regulates Fc_γReceptor-mediated Phagocytosis through the Activation and Phosphorylation of Wiskott-Aldrich Syndrome Protein (WASP) and Neural-WASP