Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 10

Publication Record

Connections

PI(3,5)P2 controls endosomal branched actin dynamics by regulating cortactin-actin interactions.
Hong NH, Qi A, Weaver AM
(2015) J Cell Biol 210: 753-69
MeSH Terms: Actin-Related Protein 2-3 Complex, Actins, Binding Sites, Cell Line, Tumor, Cortactin, Endosomes, Enzyme Activation, HeLa Cells, Humans, Phosphatidylinositol Phosphates, Protein Binding, Protein Structure, Tertiary, RNA Interference, RNA, Small Interfering, Wiskott-Aldrich Syndrome Protein, Neuronal, rab GTP-Binding Proteins
Show Abstract · Added February 15, 2016
Branched actin critically contributes to membrane trafficking by regulating membrane curvature, dynamics, fission, and transport. However, how actin dynamics are controlled at membranes is poorly understood. Here, we identify the branched actin regulator cortactin as a direct binding partner of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) and demonstrate that their interaction promotes turnover of late endosomal actin. In vitro biochemical studies indicated that cortactin binds PI(3,5)P2 via its actin filament-binding region. Furthermore, PI(3,5)P2 competed with actin filaments for binding to cortactin, thereby antagonizing cortactin activity. These findings suggest that PI(3,5)P2 formation on endosomes may remove cortactin from endosome-associated branched actin. Indeed, inhibition of PI(3,5)P2 production led to cortactin accumulation and actin stabilization on Rab7(+) endosomes. Conversely, inhibition of Arp2/3 complex activity greatly reduced cortactin localization to late endosomes. Knockdown of cortactin reversed PI(3,5)P2-inhibitor-induced actin accumulation and stabilization on endosomes. These data suggest a model in which PI(3,5)P2 binding removes cortactin from late endosomal branched actin networks and thereby promotes net actin turnover.
© 2015 Hong et al.
1 Communities
1 Members
0 Resources
16 MeSH Terms
WAVE2 regulates epithelial morphology and cadherin isoform switching through regulation of Twist and Abl.
Bryce NS, Reynolds AB, Koleske AJ, Weaver AM
(2013) PLoS One 8: e64533
MeSH Terms: Cadherins, Epithelial-Mesenchymal Transition, Humans, Nuclear Proteins, Protein Isoforms, Proto-Oncogene Proteins c-abl, Real-Time Polymerase Chain Reaction, Twist-Related Protein 1, Wiskott-Aldrich Syndrome Protein Family
Show Abstract · Added March 5, 2014
BACKGROUND - Epithelial morphogenesis is a dynamic process that involves coordination of signaling and actin cytoskeletal rearrangements.
PRINCIPAL FINDINGS - We analyzed the contribution of the branched actin regulator WAVE2 in the development of 3-dimensional (3D) epithelial structures. WAVE2-knockdown (WAVE2-KD) cells formed large multi-lobular acini that continued to proliferate at an abnormally late stage compared to control acini. Immunostaining of the cell-cell junctions of WAVE2-KD acini revealed weak and heterogeneous E-cadherin staining despite little change in actin filament localization to the same junctions. Analysis of cadherin expression demonstrated a decrease in E-cadherin and an increase in N-cadherin protein and mRNA abundance in total cell lysates. In addition, WAVE2-KD cells exhibited an increase in the mRNA levels of the epithelial-mesenchymal transition (EMT)-associated transcription factor Twist1. KD of Twist1 expression in WAVE2-KD cells reversed the cadherin switching and completely rescued the aberrant 3D morphological phenotype. Activity of the WAVE2 complex binding partner Abl kinase was also increased in WAVE2-KD cells, as assessed by tyrosine phosphorylation of the Abl substrate CrkL. Inhibition of Abl with STI571 rescued the multi-lobular WAVE2-KD 3D phenotype whereas overexpression of Abl kinase phenocopied the WAVE2-KD phenotype.
CONCLUSIONS - The WAVE2 complex regulates breast epithelial morphology by a complex mechanism involving repression of Twist1 expression and Abl kinase activity. These data reveal a critical role for WAVE2 complex in regulation of cellular signaling and epithelial morphogenesis.
2 Communities
2 Members
0 Resources
9 MeSH Terms
Cell-cell fusion: a new function for invadosomes.
Sung BH, Weaver A
(2011) Curr Biol 21: R121-3
MeSH Terms: Actins, Animals, Cell Membrane, Cell Surface Extensions, Drosophila, Drosophila Proteins, Membrane Fusion, Microfilament Proteins, Models, Biological, Wiskott-Aldrich Syndrome Protein
Show Abstract · Added May 19, 2014
Podosomes are cytoskeletal-based structures involved in extracellular matrix remodeling and cellular motility. A new study now implicates podosomes in pore formation during myoblast fusion.
Copyright © 2011 Elsevier Ltd. All rights reserved.
0 Communities
1 Members
0 Resources
10 MeSH Terms
Cortactin: a multifunctional regulator of cellular invasiveness.
Kirkbride KC, Sung BH, Sinha S, Weaver AM
(2011) Cell Adh Migr 5: 187-98
MeSH Terms: Actin Cytoskeleton, Actin-Related Protein 2, Actin-Related Protein 3, Actins, Animals, Binding Sites, Biomarkers, Tumor, Cell Communication, Cell Movement, Cortactin, Cytoskeleton, Female, Gene Expression, Humans, Mice, Neoplasms, Polymerization, Protein Binding, Protein Structure, Tertiary, Signal Transduction, Wiskott-Aldrich Syndrome Protein Family
Show Abstract · Added March 5, 2014
Branched actin assembly is critical for a variety of cellular processes that underlie cell motility and invasion, including cellular protrusion formation and membrane trafficking. Activation of branched actin assembly occurs at various subcellular locations via site-specific activation of distinct WASp family proteins and the Arp2/3 complex. A key branched actin regulator that promotes cell motility and links signaling, cytoskeletal and membrane trafficking proteins is the Src kinase substrate and Arp2/3 binding protein cortactin. Due to its frequent overexpression in advanced, invasive cancers and its general role in regulating branched actin assembly at multiple cellular locations, cortactin has been the subject of intense study. Recent studies suggest that cortactin has a complex role in cellular migration and invasion, promoting both on-site actin polymerization and modulation of autocrine secretion. Diverse cellular activities may derive from the interaction of cortactin with site-specific binding partners.
1 Communities
1 Members
0 Resources
21 MeSH Terms
N-wasp and the arp2/3 complex are critical regulators of actin in the development of dendritic spines and synapses.
Wegner AM, Nebhan CA, Hu L, Majumdar D, Meier KM, Weaver AM, Webb DJ
(2008) J Biol Chem 283: 15912-20
MeSH Terms: Actin-Related Protein 2-3 Complex, Amino Acid Sequence, Animals, Carbazoles, Cattle, Cell Line, Dendritic Spines, Hippocampus, Humans, Propanolamines, Protein Structure, Tertiary, Rats, Sequence Deletion, Signal Transduction, Synapses, Wiskott-Aldrich Syndrome Protein, Neuronal, cdc42 GTP-Binding Protein
Show Abstract · Added March 5, 2014
Changes in the number, size, and shape of dendritic spines are associated with synaptic plasticity, which underlies cognitive functions such as learning and memory. This plasticity is attributed to reorganization of actin, but the molecular signals that regulate this process are poorly understood. In this study, we show neural Wiskott-Aldrich syndrome protein (N-WASP) regulates the formation of dendritic spines and synapses in hippocampal neurons. N-WASP localized to spines and active, functional synapses as shown by loading with FM4-64 dye. Knock down of endogenous N-WASP expression by RNA interference or inhibition of its activity by treatment with a specific inhibitor, wiskostatin, caused a significant decrease in the number of spines and excitatory synapses. Deletion of the C-terminal VCA region of N-WASP, which binds and activates the actin-related protein 2/3 (Arp2/3) complex, dramatically decreased the number of spines and synapses, suggesting activation of the Arp2/3 complex is critical for spine and synapse formation. Consistent with this, Arp3, like N-WASP, was enriched in spines and excitatory synapses and knock down of Arp3 expression impaired spine and synapse formation. A similar defect in spine and synapse formation was observed when expression of an N-WASP activator, Cdc42, was knocked down. Thus, activation of N-WASP and, subsequently, the Arp2/3 complex appears to be an important molecular signal for regulating spines and synapses. Arp2/3-mediated branching of actin could be a mechanism by which dendritic spine heads enlarge and subsequently mature. Collectively, our results point to a critical role for N-WASP and the Arp2/3 complex in spine and synapse formation.
1 Communities
2 Members
0 Resources
17 MeSH Terms
Waved-1 mutant mice are hypersensitive to the locomotor actions of cocaine.
Stanwood GD, Levitt P
(2007) Synapse 61: 259-62
MeSH Terms: Analysis of Variance, Animals, Behavior, Animal, Cocaine, Dopamine Uptake Inhibitors, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Motor Activity, Stereotyped Behavior, Wiskott-Aldrich Syndrome Protein Family
Show Abstract · Added January 20, 2015
Transforming growth factor-alpha (TGFalpha) is a well-known regulator of many developmental processes, and is expressed heavily in basal forebrain and striatal regions. When TGFalpha is reduced in Waved-1 (Wa-1) mutant mice, brain anatomy, biogenic amines, stress response, and behavior are normal prior to, but altered following puberty. As an initial screen for possible alterations in nigrostriatal and mesolimbic dopamine (DA) systems, we tested adult Wa-1 mutant mice in an open field, following acute injection with cocaine (15 mg/kg). Wa-1 mice exhibited significantly greater ambulatory distance, number of ambulatory episodes, and cocaine-induced motor stereotypies than do controls. These data indicate that adult Wa-1 mice are hypersensitive to the locomotor effects of cocaine and provide a new potential link between neurodevelopmental processes and adult psychostimulant responsiveness.
0 Communities
1 Members
0 Resources
11 MeSH Terms
Integration of signals to the Arp2/3 complex.
Weaver AM, Young ME, Lee WL, Cooper JA
(2003) Curr Opin Cell Biol 15: 23-30
MeSH Terms: Actin Cytoskeleton, Actin-Related Protein 2, Actin-Related Protein 3, Animals, Cortactin, Cytoskeletal Proteins, Eukaryotic Cells, Humans, Microfilament Proteins, Proteins, Signal Transduction, Wiskott-Aldrich Syndrome Protein
Show Abstract · Added March 5, 2014
The Arp2/3 complex is necessary for nucleating the formation of branched networks of actin filaments at the cell cortex, and an increasing number of proteins able to activate the Arp2/3 complex have been described. The Wiskott-Aldrich syndrome protein (WASP) family and cortactin comprise the large majority of the known activators. WASPs bind to Arp2/3 via an acidic (A) domain, and a WH2 domain appears to bring an actin monomer to Arp2/3, promoting the nucleation of the new filament. Cortactin also binds the Arp2/3 complex via an A domain; however, it also binds to actin filaments, which helps activate the Arp2/3 complex and stabilise the newly created branches between the filaments.
0 Communities
1 Members
0 Resources
12 MeSH Terms
Interaction of cortactin and N-WASp with Arp2/3 complex.
Weaver AM, Heuser JE, Karginov AV, Lee WL, Parsons JT, Cooper JA
(2002) Curr Biol 12: 1270-8
MeSH Terms: Actin-Related Protein 2, Actin-Related Protein 3, Actins, Amino Acid Sequence, Animals, Binding Sites, Brain, Cattle, Chickens, Cortactin, Cytoskeletal Proteins, Kinetics, Microfilament Proteins, Molecular Sequence Data, Mutagenesis, Site-Directed, Nerve Tissue Proteins, Protein Conformation, Recombinant Fusion Proteins, Signal Transduction, Thymus Gland, Tryptophan, Wiskott-Aldrich Syndrome, Wiskott-Aldrich Syndrome Protein, Neuronal
Show Abstract · Added March 5, 2014
BACKGROUND - Dynamic actin assembly is required for diverse cellular processes and often involves activation of Arp2/3 complex. Cortactin and N-WASp activate Arp2/3 complex, alone or in concert. Both cortactin and N-WASp contain an acidic (A) domain that is required for Arp2/3 complex binding.
RESULTS - We investigated how cortactin and the constitutively active VCA domain of N-WASp interact with Arp2/3 complex. Structural studies showed that cortactin is a thin, elongated monomer. Chemical crosslinking studies demonstrated selective interaction of the Arp2/3 binding NTA domain of cortactin (cortactin NTA) with the Arp3 subunit and VCA with Arp3, Arp2, and ARPC1/p40. Cortactin NTA and VCA crosslinking to the Arp3 subunit were mutually exclusive; however, cortactin NTA did not inhibit VCA crosslinking to Arp2 or ARPC1/p40, nor did it inhibit activation of Arp2/3 complex by VCA. We conducted an experiment in which a saturating concentration of cortactin NTA modestly lowered the binding affinity of VCA for Arp2/3; the results of this experiment provided further evidence for ternary complex formation. Consistent with a common binding site on Arp3, a saturating concentration of VCA abolished binding of cortactin to Arp2/3 complex.
CONCLUSIONS - Under certain circumstances, cortactin and N-WASp can bind simultaneously to Arp2/3 complex, accounting for their synergy in activation of actin assembly. The interaction of cortactin NTA with Arp2/3 complex does not inhibit Arp2/3 activation by N-WASp, despite competition for a common binding site located on the Arp3 subunit. These results suggest a model in which cortactin may bridge Arp2/3 complex to actin filaments via Arp3 and N-WASp activates Arp2/3 complex by binding Arp2 and/or ARPC1/p40.
0 Communities
1 Members
0 Resources
23 MeSH Terms
Cortactin promotes and stabilizes Arp2/3-induced actin filament network formation.
Weaver AM, Karginov AV, Kinley AW, Weed SA, Li Y, Parsons JT, Cooper JA
(2001) Curr Biol 11: 370-4
MeSH Terms: Actin Cytoskeleton, Actin-Related Protein 2, Actin-Related Protein 3, Actins, Animals, Binding Sites, Cattle, Cortactin, Cytoskeletal Proteins, Microfilament Proteins, Nerve Tissue Proteins, Recombinant Fusion Proteins, Wiskott-Aldrich Syndrome Protein, Neuronal, src Homology Domains
Show Abstract · Added March 5, 2014
Cortactin is a c-src substrate associated with sites of dynamic actin assembly at the leading edge of migrating cells. We previously showed that cortactin binds to Arp2/3 complex, the essential molecular machine for nucleating actin filament assembly. In this study, we demonstrate that cortactin activates Arp2/3 complex based on direct visualization of filament networks and pyrene actin assays. Strikingly, cortactin potently inhibited the debranching of filament networks. When cortactin was added in combination with the active VCA fragment of N-WASp, they synergistically enhanced Arp2/3-induced actin filament branching. The N-terminal acidic and F-actin binding domains of cortactin were both necessary to activate Arp2/3 complex. These results support a model in which cortactin modulates actin filament dendritic nucleation by two mechanisms, (1) direct activation of Arp2/3 complex and (2) stabilization of newly generated filament branch points. By these mechanisms, cortactin may promote the formation and stabilization of the actin network that drives protrusion at the leading edge of migrating cells.
0 Communities
1 Members
0 Resources
14 MeSH Terms
The Arp2/3 complex: a multifunctional actin organizer.
Machesky LM, Gould KL
(1999) Curr Opin Cell Biol 11: 117-21
MeSH Terms: Actin-Related Protein 2, Actin-Related Protein 3, Actins, Cytoskeletal Proteins, Humans, In Vitro Techniques, Models, Biological, Proteins, Wiskott-Aldrich Syndrome Protein, Yeasts
Show Abstract · Added March 5, 2014
The actin-related proteins (Arps) constitute a recently characterized family of proteins, many of which function as members of multiprotein complexes. The discovery that two family members, Arp2 and Arp3, act as multifunctional organizers of actin filaments in all eukaryotes has generated much excitement. Over the past two years, newly discovered properties of the Arp2/3 complex have suggested a central role in the control of actin polymerization. First, it promotes actin assembly on the surface of the motile intracellular pathogen Listeria monocytogenes. Second, it can nucleate and cross-link actin filaments in vitro. Third, it localizes with dynamic actin-rich spots of mammalian cells suggesting a role in protrusion; it is found in cortical actin patches in the budding and fission yeasts where it may control patch movement and cortical actin function. Clearly, the complex has a central role in actin cytoskeletal function and will be the subject of much research in the coming years.
0 Communities
1 Members
0 Resources
10 MeSH Terms