GRB2 Links Signaling to Actin Assembly by Enhancing Interaction of Neural Wiskott-Aldrich Syndrome Protein (N-WASp) with Actin-related Protein (ARP2/3) Complex

Carlier, Marie-France; Nioche, Pierre; Broutin, Isabelle; Boujemaa, Rajaa; Clainche, Christophe Le; Égile, Coumaran; Garbay, Christiane; Ducruix, A.; Sansonetti, Philippe J.; Pantaloni, Dominique

doi:10.1074/jbc.m000687200

Cited by 196 publications

(171 citation statements)

References 58 publications

(32 reference statements)

Supporting

Mentioning

159

Contrasting

Order By: Relevance

“…Magicin also associates with Grb2, which has been suggested to act not only as an adaptor but also as an effector of actin-dependent processes in response to cell signaling (Carlier et al, 2000). The direct interaction of magicin with both merlin and Grb2 adds further support for a role of merlin in receptor-mediated signaling and/or a role in the regulation of cytoskeletal reorganization.…”

Section: Introductionmentioning

confidence: 88%

Magicin, a novel cytoskeletal protein associates with the NF2 tumor suppressor merlin and Grb2

et al. 2004

View full text Add to dashboard Cite

Neurofibromatosis 2 (NF2) is a dominantly inherited disorder characterized by bilateral vestibular schwannomas and meningiomas. Merlin, the neurofibromatosis 2 tumor suppressor protein, is related to the ERM (ezrin, radixin, moesin) proteins and, like its family members, is thought to play a role in plasma membrane-cytoskeletal interactions. We report a novel protein as a merlin-specific binding partner that we have named magicin (merlin and Grb2 interacting cytoskeletal protein) and show that the two proteins interact in vitro and in vivo as well as colocalize beneath the plasma membrane. Magicin is a 24 kDa protein that is expressed in many cell lines and tissues. Magicin, similar to merlin, associates with the actin cytoskeleton as determined by cofractionation, immunofluorescence and electron microscopy. Analysis of the magicin sequence reveals binding motifs for the adaptor protein Grb2. Employing affinity binding, blot overlay and co-immunoprecipitation assays, we demonstrate an interaction between Grb2 and magicin. In addition, merlin is capable of forming a ternary complex with magicin and Grb2. These results support a role for merlin in receptor-mediated signaling at the cell surface, and may have implications in the regulation of cytoskeletal reorganization.

show abstract

Section: Introductionmentioning

confidence: 88%

Magicin, a novel cytoskeletal protein associates with the NF2 tumor suppressor merlin and Grb2

et al. 2004

View full text Add to dashboard Cite

show abstract

“…Instead, the proline-rich region of WASP is necessary and sufficient to mediate recruitment. Many Src homology 3 (SH3) domain-containing proteins including Lck, Fyn, Btk, Itk, Nck, Grb2, Profilin, and proline, serine, threonine phosphatase interacting protein (PST-PIP) have been shown to interact with the proline-rich domain of WASP in vitro (23)(24)(25)(26)(27)(28)(29). However, the protein responsible for WASP recruitment during T cell signaling is not known.…”

mentioning

confidence: 99%

SLP-76 Coordinates Nck-Dependent Wiskott-Aldrich Syndrome Protein Recruitment with Vav-1/Cdc42-Dependent Wiskott-Aldrich Syndrome Protein Activation at the T Cell-APC Contact Site

Zeng

Cannon

Abraham

et al. 2003

The Journal of Immunology

156

148

View full text Add to dashboard Cite

We have shown previously that Wiskott-Aldrich syndrome protein (WASP) activation at the site of T cell-APC interaction is a two-step process, with recruitment dependent on the proline-rich domain and activation dependent on binding of Cdc42-GTP to the GTPase binding domain. Here, we show that WASP recruitment occurs through binding to the C-terminal Src homology 3 domain of Nck. In contrast, WASP activation requires Vav-1. In Vav-1-deficient T cells, WASP recruitment proceeds normally, but localized activation of Cdc42 and WASP is disrupted. The recruitment and activation of WASP are coordinated by tyrosine-phosphorylated Src homology 2 domain-containing leukocyte protein of 76 kDa, which functions as a scaffold, bringing Nck and WASP into proximity with Vav-1 and Cdc42-GTP. Taken together, these findings reconstruct the signaling pathway leading from TCR ligation to localized WASP activation.

show abstract

“…The ubiquitously expressed N-WASP (neuronal WASP) is a modular protein autoinhibited by an intramolecular interaction in its inactive state. Binding of specific molecules including phosphatidylinositol 4,5-bisphosphate (PIP 2 ), Cdc42, Nck, and Grb2 to N-WASP disrupts this inhibition and unmasks the WASP homology 2 and acidic (WA) domain, allowing the Arp2͞3 complex to initiate de novo actin polymerization (2)(3)(4)(5)(6). WASP, a protein found only in hematopoietic cells, is closely related to N-WASP, sharing 50% sequence similarity.…”

mentioning

confidence: 99%

Role of the WASP family proteins for Mycobacterium marinum actin tail formation

Stamm

Pak

Morisaki

et al. 2005

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

View full text Add to dashboard Cite

Mycobacterium marinum, a natural pathogen of fish and frogs and an occasional pathogen of humans, is capable of inducing actin tail formation within the cytoplasm of macrophages, leading to actinbased motility and intercellular spread. Actin tail formation by M. marinum is markedly reduced in macrophages deficient in the Wiskott-Aldrich syndrome protein (WASP), which still contain the closely related and ubiquitously expressed protein N-WASP (neuronal WASP). In fibroblasts lacking both WASP and N-WASP, M. marinum is incapable of efficient actin polymerization and of intercellular spread. By reconstituting these cells, we find that M. marinum is able to use either WASP or N-WASP to induce actin polymerization. Inhibition or genetic deletion of tyrosine phosphorylation, Nck, WASP-interacting protein, and Cdc42 does not affect M. marinum actin tail formation, excluding the participation of these molecules as upstream activators of N-WASP in the initiation of actin-based motility. In contrast, deletion of the phosphatidylinositol 4,5-bisphosphate-binding basic motif in N-WASP eliminates M. marinum actin tail formation. 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. Binding of specific molecules including phosphatidylinositol 4,5-bisphosphate (PIP 2 ), Cdc42, Nck, and Grb2 to N-WASP disrupts this inhibition and unmasks the WASP homology 2 and acidic (WA) domain, allowing the Arp2͞3 complex to initiate de novo actin polymerization (2-6). WASP, a protein found only in hematopoietic cells, is closely related to N-WASP, sharing 50% sequence similarity. The two proteins are similarly organized and are controlled by the same host cell inputs. Less related to N-WASP are the WAVE proteins that contain the WA domain output region but have different activating inputs (7).Diverse pathogens have evolved mechanisms to hijack this Arp2͞ 3-dependent pathway of actin polymerization for their own benefit (reviewed in ref. 8). For vaccinia virus, actin polymerization is required for viral egress from infected cells. Enterohemorrhagic and enteropathogenic Escherichia coli species' actin polymerization leads to pedestal formation, causing attachment and effacement lesions on gut epithelia. For Listeria, Shigella, Burkholderia, Rickettsia, and Mycobacterium marinum, actin polymerization on the surface of cytoplasmic bacteria results in actin tails, intracellular motility, and direct intercellular spread. Interestingly, these pathogens use independently evolved proteins to target different steps leading to Arp2͞3 activation. Listeria, Rickettsia, and perhaps Burkholderia mimic host cell N-WASP to activate the Arp2͞3 complex directly, and actin tail formation by these species is independent of host cell N-WASP (9-14). The other pathogens depend on the WASP family for actin polymerization: Shigella and enterohemorrhagic E. coli (EHEC) have molecules that directly recruit...

show abstract

GRB2 Links Signaling to Actin Assembly by Enhancing Interaction of Neural Wiskott-Aldrich Syndrome Protein (N-WASp) with Actin-related Protein (ARP2/3) Complex

Cited by 196 publications

References 58 publications

Magicin, a novel cytoskeletal protein associates with the NF2 tumor suppressor merlin and Grb2

Magicin, a novel cytoskeletal protein associates with the NF2 tumor suppressor merlin and Grb2

SLP-76 Coordinates Nck-Dependent Wiskott-Aldrich Syndrome Protein Recruitment with Vav-1/Cdc42-Dependent Wiskott-Aldrich Syndrome Protein Activation at the T Cell-APC Contact Site

Role of the WASP family proteins for Mycobacterium marinum actin tail formation

Contact Info

Product

Resources

About