scholarly journals Syndapin I, a Synaptic Dynamin-binding Protein that Associates with the Neural Wiskott-Aldrich Syndrome Protein

1999 ◽  
Vol 10 (2) ◽  
pp. 501-513 ◽  
Author(s):  
Britta Qualmann ◽  
Jack Roos ◽  
Paul J. DiGregorio ◽  
Regis B. Kelly
Keyword(s):  
Synaptic Vesicle ◽  
Nerve Terminal ◽  
Specific Interaction ◽  
Sh3 Domain ◽  
High Molecular Weight Complex ◽  
Wiskott Aldrich Syndrome ◽  
C Terminus ◽  
Dynamin I ◽  
Syndrome Protein

The GTPase dynamin has been clearly implicated in clathrin-mediated endocytosis of synaptic vesicle membranes at the presynaptic nerve terminal. Here we describe a novel 52-kDa protein in rat brain that binds the proline-rich C terminus of dynamin. Syndapin I (synaptic, dynamin-associated protein I) is highly enriched in brain where it exists in a high molecular weight complex. Syndapin I can be involved in multiple protein–protein interactions via a src homology 3 (SH3) domain at the C terminus and two predicted coiled-coil stretches. Coprecipitation studies and blot overlay analyses revealed that syndapin I binds the brain-specific proteins dynamin I, synaptojanin, and synapsin I via an SH3 domain-specific interaction. Coimmunoprecipitation of dynamin I with antibodies recognizing syndapin I and colocalization of syndapin I with dynamin I at vesicular structures in primary neurons indicate that syndapin I associates with dynamin I in vivo and may play a role in synaptic vesicle endocytosis. Furthermore, syndapin I associates with the neural Wiskott-Aldrich syndrome protein, an actin-depolymerizing protein that regulates cytoskeletal rearrangement. These characteristics of syndapin I suggest a molecular link between cytoskeletal dynamics and synaptic vesicle recycling in the nerve terminal.

CrkL is an adapter for Wiskott-Aldrich syndrome protein and Syk

Blood ◽  
2001 ◽  
Vol 97 (9) ◽  
pp. 2633-2639 ◽  
Author(s):  
Atsushi Oda ◽  
Hans D. Ochs ◽  
Laurence A. Lasky ◽  
Susan Spencer ◽  
Katsutoshi Ozaki ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Tyrosine Phosphorylation ◽  
Sh3 Domain ◽  
Cytoskeletal Proteins ◽  
Kinase Assay ◽  
Sh3 Domains ◽  
Wiskott Aldrich Syndrome ◽  
Dynamic Cell ◽  
Syndrome Protein

Abstract Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia are caused by mutations of the WAS protein (WASP) gene. WASP may be involved in the regulation of podosome, an actin-rich dynamic cell adhesion structure formed by various types of cells. The molecular links between WASP and podosomes or other cell adhesion structures are unknown. Platelets express an SH2-SH3 adapter molecule, CrkL, that can directly associate with paxillin, which is localized in podosomes. The hypothesis that CrkL binds to WASP was, therefore, tested. Results from coprecipitation experiments using anti-CrkL and GST-fusion proteins suggest that CrkL binds to WASP through its SH3 domain and that the binding was not affected by WASP tyrosine phosphorylation. The binding of GST-fusion SH3 domain of PSTPIP1 in vitro was also not affected by WASP tyrosine phosphorylation, suggesting that the binding of the SH3 domains to WASP is not inhibited by tyrosine phosphorylation of WASP. Anti-CrkL also coprecipitates a 72-kd protein, which was identified as syk tyrosine kinase, critical for collagen induced-platelet activation. CrkL immunoprecipitates contain kinase-active syk, as evidenced by an in vitro kinase assay. Coprecipitation experiments using GST-fusion CrkL proteins suggest that both SH2 and SH3 domains of CrkL are involved in the binding of CrkL to syk. WASP, CrkL, syk, and paxillin-like Hic-5 incorporated to platelet cytoskeleton after platelet aggregation. Thus, CrkL is a novel molecular adapter for WASP and syk and may potentially transfer these molecules to the cytoskeleton through association with cytoskeletal proteins such as Hic-5.

scholarly journals TheSaccharomyces cerevisiaeHomologue of Human Wiskott–Aldrich Syndrome Protein Las17p Interacts with the Arp2/3 Complex

1999 ◽  
Vol 10 (10) ◽  
pp. 3521-3538 ◽  
Author(s):  
Ammar Madania ◽  
Pascal Dumoulin ◽  
Sandrine Grava ◽  
Hiroko Kitamoto ◽  
Claudia Schärer-Brodbeck ◽  
...  
Keyword(s):  
Actin Polymerization ◽  
Temperature Sensitive ◽  
Multicopy Suppressor ◽  
Wiskott Aldrich Syndrome ◽  
Regulatory Cascades ◽  
Src Homology ◽  
Synthetically Lethal ◽  
Actin Patch ◽  
Syndrome Protein

Yeast Las17 protein is homologous to the Wiskott–Aldrich Syndrome protein, which is implicated in severe immunodeficiency. Las17p/Bee1p has been shown to be important for actin patch assembly and actin polymerization. Here we show that Las17p interacts with the Arp2/3 complex. LAS17 is an allele-specific multicopy suppressor of ARP2 and ARP3 mutations; overexpression restores both actin patch organization and endocytosis defects in ARP2 temperature-sensitive (ts) cells. Six of seven ARP2 ts mutants and at least oneARP3 ts mutant are synthetically lethal withlas17Δ ts confirming functional interaction with the Arp2/3 complex. Further characterization of las17Δcells showed that receptor-mediated internalization of α factor by the Ste2 receptor is severely defective. The polarity of normal bipolar bud site selection is lost. Las17-gfp remains localized in cortical patches in vivo independently of polymerized actin and is required for the polarized localization of Arp2/3 as well as actin. Coimmunoprecipitation of Arp2p with Las17p indicates that Las17p interacts directly with the complex. Two hybrid results also suggest that Las17p interacts with actin, verprolin, Rvs167p and several other proteins including Src homology 3 (SH3) domain proteins, suggesting that Las17p may integrate signals from different regulatory cascades destined for the Arp2/3p complex and the actin cytoskeleton.

scholarly journals A novel Wiskott-Aldrich syndrome protein (WASP) complex mutation identified in a WAS patient results in an aberrant product at the C-terminus from two transcripts with unusual polyA signals

2005 ◽  
Vol 51 (2) ◽  
pp. 92-97 ◽  
Author(s):  
Nuria Andreu ◽  
Maricruz García-Rodríguez ◽  
Victor Volpini ◽  
Cecilia Frecha ◽  
Ignacio J. Molina ◽  
...  
Keyword(s):  
Wiskott Aldrich Syndrome ◽  
C Terminus ◽  
Complex Mutation ◽  
Syndrome Protein

scholarly journals Wiskott-Aldrich syndrome protein physically associates with Nck through Src homology 3 domains.

1995 ◽  
Vol 15 (10) ◽  
pp. 5725-5731 ◽  
Author(s):  
O M Rivero-Lezcano ◽  
A Marcilla ◽  
J H Sameshima ◽  
K C Robbins
Keyword(s):  
Specific Interaction ◽  
Protein Product ◽  
In Vitro Translation ◽  
Cdna Expression Library ◽  
Cytosol Fraction ◽  
Wiskott Aldrich Syndrome ◽  
Src Homology 3 ◽  
Src Homology ◽  
Syndrome Protein

In the second of a series of experiments designed to identify p47nck-Src homology 3 (SH3)-binding molecules, we report the cloning of SAKAP II (Src A box Nck-associated protein II) from an HL60 cDNA expression library. This molecule has been identified as a cDNA encoding the protein product of WASP, which is mutated in Wiskott-Aldrich syndrome patients. Studies in vivo and in vitro demonstrated a highly specific interaction between the SH3 domains of p47nck and Wiskott-Aldrich syndrome protein. Furthermore, anti-Wiskott-Aldrich syndrome protein antibodies recognized a protein of 66 kDa by Western blot (immunoblot) analysis. In vitro translation studies identified the 66-kDa protein as the protein product of WASP, and subcellular fractionation experiments showed that p66WASP is mainly present in the cytosol fraction, although significant amounts are also present in membrane and nuclear fractions. The main p47nck region implicated in the association with p66WASP was found to be the carboxy-terminal SH3 domain.

scholarly journals IL-2 in the tumor microenvironment is necessary for Wiskott-Aldrich syndrome protein deficient NK cells to respond to tumors in vivo

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Joanna S. Kritikou ◽  
Carin I. M. Dahlberg ◽  
Marisa A. P. Baptista ◽  
Arnika K. Wagner ◽  
Pinaki P. Banerjee ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Nk Cells ◽  
Wiskott Aldrich Syndrome ◽  
Syndrome Protein

scholarly journals Abelson Interactor 1 (Abi1) and Its Interaction with Wiskott-Aldrich Syndrome Protein (Wasp) Are Critical for Proper Eye Formation in Xenopus Embryos

2013 ◽  
Vol 288 (20) ◽  
pp. 14135-14146 ◽  
Author(s):  
Arvinder Singh ◽  
Emily F. Winterbottom ◽  
Yon Ju Ji ◽  
Yoo-Seok Hwang ◽  
Ira O. Daar
Keyword(s):  
Progenitor Cells ◽  
Cultured Cells ◽  
Scaffold Protein ◽  
Wiskott Aldrich Syndrome ◽  
Src Homology 3 ◽  
Eye Field ◽  
Src Homology 3 Domain ◽  
Src Homology ◽  
Syndrome Protein

Abl interactor 1 (Abi1) is a scaffold protein that plays a central role in the regulation of actin cytoskeleton dynamics as a constituent of several key protein complexes, and homozygous loss of this protein leads to embryonic lethality in mice. Because this scaffold protein has been shown in cultured cells to be a critical component of pathways controlling cell migration and actin regulation at cell-cell contacts, we were interested to investigate the in vivo role of Abi1 in morphogenesis during the development of Xenopus embryos. Using morpholino-mediated translation inhibition, we demonstrate that knockdown of Abi1 in the whole embryo, or specifically in eye field progenitor cells, leads to disruption of eye morphogenesis. Moreover, signaling through the Src homology 3 domain of Abi1 is critical for proper movement of retinal progenitor cells into the eye field and their appropriate differentiation, and this process is dependent upon an interaction with the nucleation-promoting factor Wasp (Wiskott-Aldrich syndrome protein). Collectively, our data demonstrate that the Abi1 scaffold protein is an essential regulator of cell movement processes required for normal eye development in Xenopus embryos and specifically requires an Src homology 3 domain-dependent interaction with Wasp to regulate this complex morphogenetic process.

Involvement of Wiskott-Aldrich Syndrome Protein in B-Cell Cytoplasmic Tyrosine Kinase Pathway

Blood ◽  
1999 ◽  
Vol 93 (6) ◽  
pp. 2003-2012 ◽  
Author(s):  
Yoshihiro Baba ◽  
Shigeaki Nonoyama ◽  
Masato Matsushita ◽  
Tomoki Yamadori ◽  
Shoji Hashimoto ◽  
...  
Keyword(s):  
B Cells ◽  
Tyrosine Kinase ◽  
B Cell ◽  
B Lymphocyte ◽  
Phosphorylation Site ◽  
Cellular Protein ◽  
Exact Nature ◽  
Wiskott Aldrich Syndrome ◽  
Syndrome Protein

Bruton’s tyrosine kinase (Btk) has been shown to play a role in normal B-lymphocyte development. Defective expression of Btk leads to human and murine immunodeficiencies. However, the exact role of Btk in the cytoplasmic signal transduction in B cells is still unclear. This study represents a search for the substrate for Btk in vivo. We identified one of the major phosphoproteins associated with Btk in the preB cell line NALM6 as the Wiskott-Aldrich syndrome protein (WASP), the gene product responsible for Wiskott-Aldrich syndrome, which is another hereditary immunodeficiency with distinct abnormalities in hematopoietic cells. We demonstrated that WASP was transiently tyrosine-phosphorylated after B-cell antigen receptor cross-linking on B cells, suggesting that WASP is located downstream of cytoplasmic tyrosine kinases. An in vivo reconstitution system demonstrated that WASP is physically associated with Btk and can serve as the substrate for Btk. A protein binding assay suggested that the tyrosine-phosphorylation of WASP alters the association between WASP and a cellular protein. Furthermore, identification of the phosphorylation site of WASP in reconstituted cells allowed us to evaluate the catalytic specificity of Btk, the exact nature of which is still unknown.

641 Neural Wiskott-Aldrich Syndrome Protein is Required for the Pathogenesis of Citrobacter rodentium In Vivo

2010 ◽  
Vol 138 (5) ◽  
pp. S-84-S-85
Author(s):  
John J. Garber ◽  
Hai Ning Shi ◽  
Deanna D. Nguyen ◽  
Michel H. Maillard ◽  
Scott B. Snapper
Keyword(s):  
Citrobacter Rodentium ◽  
Wiskott Aldrich Syndrome ◽  
Syndrome Protein

scholarly journals In Vivo Chronic Stimulation Unveils Autoreactive Potential of Wiskott–Aldrich Syndrome Protein-Deficient B Cells

2017 ◽  
Vol 8 ◽  
Author(s):  
Maria Carmina Castiello ◽  
Francesca Pala ◽  
Lucia Sereni ◽  
Elena Draghici ◽  
Donato Inverso ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Stimulation ◽  
Wiskott Aldrich Syndrome ◽  
Syndrome Protein
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