N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility

@article{Snapper2001NWASPDR,
  title={N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility},
  author={Scott B. Snapper and Fuminao Takeshima and In{\'e}s Mar{\'i}a Ant{\'o}n and Ching-Hui Liu and Sheila M. Thomas and Deanna D. Nguyen and Darryll D. Dudley and Hunter B. Fraser and Daniel L. Purich and Marco A L{\'o}pez-Ilasaca and Christoph Klein and Laurie Davidson and Roderick T Bronson and Richard C. Mulligan and Frederick Seacrest Southwick and Raif S. Geha and Marcia B. Goldberg and Fred S. Rosen and John H. Hartwig and Frederick W. Alt},
  journal={Nature Cell Biology},
  year={2001},
  volume={3},
  pages={897-904}
}
The Wiskott–Aldrich syndrome protein (WASP) family of molecules integrates upstream signalling events with changes in the actin cytoskeleton. N-WASP has been implicated both in the formation of cell-surface projections (filopodia) required for cell movement and in the actin-based motility of intracellular pathogens. To examine N-WASP function we have used homologous recombination to inactivate the gene encoding murine N-WASP. Whereas N-WASP-deficient embryos survive beyond gastrulation and… Expand
N-WASP has the ability to compensate for the loss of WASP in macrophage podosome formation and chemotaxis.
TLDR
The ability of N-WASP to partially compensate for the loss of WASP and restore actin cytoskeleton integrity is suggested to be physiologically relevant since activated murine WASP-deficient peritoneal macrophages, which show enhanced N-wASP expression, also show an increase in matrix degradation. Expand
Abi1 regulates the activity of N-WASP and WAVE in distinct actin-based processes
TLDR
It is reported that Abi1, an essential component of the WAVE protein complex, also has a critical role in regulating N-WASP-dependent function and is a dual regulator of WAVE and N- WASP activities in specific processes that are dependent on actin dynamics. Expand
Molecular difference between WASP and N-WASP critical for chemotaxis of T-cells towards SDF-1α
TLDR
It is demonstrated that the I30 region of WASP is critical for localization and chemotaxis, which suggests that N-WASP’s failure to compensate for WASP in rescuing Chemotaxis could be due to the absence of this I30 area. Expand
The non-redundant role of N-WASP in podosome-mediated matrix degradation in macrophages.
Wiskott-Aldrich Syndrome Protein (WASP) is a hematopoietic cell-specific regulator of Arp2/3-dependent actin polymerization. Despite the presence of the highly homologous N-WASP (neural-WASP),Expand
Role of the WASP family proteins for Mycobacterium marinum actin tail formation.
  • L. Stamm, M. Pak, +4 authors E. Brown
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 2005
TLDR
Together, these data demonstrate that M. marinum subversion of host actin polymerization is most similar to distantly related Gram-negative organisms but that its mechanism for activating WASP family proteins is unique. Expand
The rate of N-WASP exchange limits the extent of ARP2/3-complex-dependent actin-based motility
TLDR
It is suggested that the exchange rate of N-WASP controls the rate of ARP2/3-complex-dependent actin-based motility by regulating the extent of actin polymerization by antagonizing filament capping. Expand
The role of Wiskott-Aldrich Syndrome protein-mediated actin dynamics in controlling type-I IFN production in plasmacytoid dendritic cells
TLDR
It is shown that pDCs from WKO animals are chronically activated, secrete type-I IFN constitutively and become refractory to further stimulation in vivo and that WASp-mediated actin dynamics control the activation of the TLR9/IFN-α pathway in a cell autonomous fashion. Expand
A WASp Homolog Powers Actin Polymerization-Dependent Motility of Endosomes In Vivo
TLDR
Fluorescence video microscopy of yeast cells expressing a GFP-tagged G protein-coupled receptor (Ste2-GFP) as an endocytic marker revealed that endosomes and the lysosome-like vacuole are highly motile. Expand
Abl Kinases Regulate Actin Comet Tail Elongation via an N-WASP-Dependent Pathway
TLDR
It is shown that the Abl kinases are required for Shigella actin comet tail formation, maximal intracellular motility, and cell-to-cell spread and a new role for Abl family kinases in the regulation of pathogen motility is uncovered. Expand
Nck- and N-WASP-dependent actin-based motility is conserved in divergent vertebrate poxviruses.
TLDR
It is found that the YLDV protein YL126 can functionally replace A36 to promote Nck- and N-WASP-dependent actin polymerization, suggesting that actin-based motility represents a common mechanism to enhance the cell-to-cell spread of vertebrate poxviruses. Expand
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References

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Neural Wiskott–Aldrich syndrome protein is implicated in the actin‐based motility of Shigella flexneri
TLDR
It is shown that neural Wiskott–Aldrich syndrome protein (N‐WASP), which is a critical target for filopodium formation downstream of Cdc42, is required for assembly of the actin tail generated by intracellular S.flexneri. Expand
A complex of N-WASP and WIP integrates signalling cascades that lead to actin polymerization
TLDR
The amino-terminal WH1 domain of N-WASP is responsible for its recruitment to sites of actin polymerization during Cdc42-independent, actin-based motility of vaccinia virus. Expand
WIP regulates N-WASP-mediated actin polymerization and filopodium formation
TLDR
It is shown that WASP-interacting protein (WIP) interacts directly with N-WASP and actin, which is consistent with their role in actin-tail formation in cells infected with vaccinia virus or Shigella. Expand
SCAR, a WASP-related Protein, Isolated as a Suppressor of Receptor Defects in Late Dictyostelium Development
TLDR
Data suggest that SCAR may be a conserved negative regulator of G protein-coupled signaling, and that it plays an important role in regulating the actin cytoskeleton. Expand
Actin-based motility of vaccinia virus mimics receptor tyrosine kinase signalling
TLDR
It is suggested that vaccinia virus spreads by mimicking the signalling pathways that are normally involved in actin polymerization at the plasma membrane, including Nck and N-WASP. Expand
Induction of filopodium formation by a WASP-related actin-depolymerizing protein N-WASP
TLDR
It is demonstrated that before it can induce filopodium formation, Cdc42 must bind a WASP-related protein, N-WASP, that is richest in neural tissues but is expressed ubiquitously. Expand
Reconstitution of actin-based motility of Listeria and Shigella using pure proteins
TLDR
Pure components of the actin cytoskeleton are used to reconstitute sustained movement in Listeria and Shigella in vitro and have implications for the understanding of the mechanism of actin-based motility in cells. Expand
The Wiskott–Aldrich syndrome protein directs actin-based motility by stimulating actin nucleation with the Arp2/3 complex
TLDR
It is demonstrated that WASP is sufficient to direct actin-based motility in cell extracts and that this function is mediated by the Arp2/3 complex. Expand
Activation of the Cdc42 Effector N-Wasp by the Shigella flexneri Icsa Protein Promotes Actin Nucleation by Arp2/3 Complex and Bacterial Actin-Based Motility
TLDR
It is shown here that the bacterial protein IcsA binds N-WASP and activates it in a Cdc42-like fashion, which unmasks two domains acting together in insertional actin polymerization. Expand
N‐WASP, a novel actin‐depolymerizing protein, regulates the cortical cytoskeletal rearrangement in a PIP2‐dependent manner downstream of tyrosine kinases.
TLDR
It is concluded that N‐WASP transmits signals from tyrosine kinases to cause a polarized rearrangement of cortical actin filaments dependent on PIP2. Expand
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