Recruitment of the Arp2/3 complex and Mena for the stimulation of actin polymerization in growth cones by nerve growth factor

Goldberg, Daniel J.; Foley, Mathew S.; Tang, Dongjiang; Grabham, Peter

doi:10.1002/(sici)1097-4547(20000515)60:4<458::aid-jnr4>3.0.co;2-z

Cited by 33 publications

(12 citation statements)

References 43 publications

(69 reference statements)

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“…The precise level of bridging between various receptors within the PSD is likely to be further complicated given the abundant alternative splicing that occurs in both Shank and Homer gene products (Lim et al, 1999;Soloviev et al, 2000). Shanks, cortactin and Arp2/3 complex are present in neuronal growth cones Goldberg et al, 2000) and given the ability to bind to both CortBP1 and Shank 3 molecular`bridges', cortactin can serve to link multiple postsynaptic receptors to sites of Arp2/3 mediated actin assembly (Figure 4). Therefore, clustering and organization of receptor components at the synapse may in part be attributable to Arp2/3 mediated actin polymerization regulated by cortactin in a manner similar to that described for the movement and formation of acetylcholine receptor clusters (Dai et al, 2000).…”

Section: Function Of Cortactin Sh3-domain Binding Proteinsmentioning

confidence: 99%

Cortactin: coupling membrane dynamics to cortical actin assembly

2001

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Exposure of cells to a variety of external signals causes rapid changes in plasma membrane morphology. Plasma membrane dynamics, including membrane ru e and microspike formation, fusion or ®ssion of intracellular vesicles, and the spatial organization of transmembrane proteins, is directly controlled by the dynamic reorganization of the underlying actin cytoskeleton. Two members of the Rho family of small GTPases, Cdc42 and Rac, have been well established as mediators of extracellular signaling events that impact cortical actin organization. Actin-based signaling through Cdc42 and Rac ultimately results in activation of the actin-related protein (Arp) 2/3 complex, which promotes the formation of branched actin networks. In addition, the activity of both receptor and non-receptor protein tyrosine kinases along with numerous actin binding proteins works in concert with Arp2/3-mediated actin polymerization in regulating the formation of dynamic cortical actin-associated structures. In this review we discuss the structure and role of the cortical actin binding protein cortactin in Rho GTPase and tyrosine kinase signaling events, with the emphasis on the roles cortactin plays in tyrosine phosphorylation-based signal transduction, regulating cortical actin assembly, transmembrane receptor organization and membrane dynamics. We also consider how aberrant regulation of cortactin levels contributes to tumor cell invasion and metastasis. Oncogene (2001) 20, 6418 ± 6434.

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Section: Function Of Cortactin Sh3-domain Binding Proteinsmentioning

confidence: 99%

Cortactin: coupling membrane dynamics to cortical actin assembly

2001

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“…N-WASP is found throughout the brain and is concentrated at nerve terminals (Fukuoka et al 1997). p34Arc and p21Arc are concentrated in the actin filaments of NGF-stimulated growth cones from rat sympathetic neurons and PC12 cells (Goldberg et al 2000). Mutations in the VCA region of N-WASP block NGF-stimulated neurite growth in PC12 cells and hippocampal neurons (Banzai et al 2000), and an N-WASP mutant incapable of binding cdc42 also blocks neurite growth (Banzai et al 2000).…”

Section: Rho Gtpases: Organizers Of Actin Structuresmentioning

confidence: 99%

“…The ena/VASP family of actin-binding proteins could contribute to these differences. Ena/VASP proteins are found at the leading edge of lamellipodia and at the tips of microspikes in fibroblasts (Nakagawa et al 2001) and are concentrated in the F-actin rich regions of NGF-stimulated sympathetic growth cones (Goldberg et al 2000). In Listeria, ena/VASP binds both ActA and actin, and is thought to link the bacterium to the actin tail .…”

Section: Rho Gtpases: Organizers Of Actin Structuresmentioning

confidence: 99%

Signaling mechanisms that regulate actin‐based motility processes in the nervous system

Meyer

Feldman

2002

Journal of Neurochemistry

171

108

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Actin-based motility is critical for nervous system development. Both the migration of neurons and the extension of neurites require organized actin polymerization to push the cell membrane forward. Numerous extracellular stimulants of motility and axon guidance cues regulate actin-based motility through the rho GTPases (rho, rac, and cdc42). The rho GTPases reorganize the actin cytoskeleton, leading to stress fiber, filopodium, or lamellipodium formation. The activity of the rho GTPases is regulated by a variety of proteins that either stimulate GTP uptake (activation) or hydrolysis (inactivation). These proteins potentially link extracellular signals to the activation state of rho GTPases. Effectors downstream of the rho GTPases that directly influence actin polymerization have been identified and are involved in neurite development.The Arp2/3 complex nucleates the formation of new actin branches that extend the membrane forward. Ena/VASP proteins can cause the formation of longer actin filaments, characteristic of growth cone actin morphology, by preventing the capping of barbed ends. Actin-depolymerizing factor (ADF)/cofilin depolymerizes and severs actin branches in older parts of the actin meshwork, freeing monomers to be re-incorporated into actively growing filaments. The signaling mechanisms by which extracellular cues that guide axons to their targets lead to direct effects on actin filament dynamics are becoming better understood. Keywords: actin-depolymerizing factor (ADF)/cofilin, actinrelated protein Arp2/3, ena/VASP, LIM kinase, rho GTPase.

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“…In C. elegans, UNC-34/Enabled acts in parallel to UNC-115/ abLIM and Rac signaling in axon guidance (Withee et al 2004;Shakir et al 2006). Other actin-modulating molecules in addition to UNC-115 are likely to act downstream of Racs, as unc-115 null mutations have very little effect on axon guidance alone but synergize with mig-2, ced-10, and unc-34 mutations.Molecules containing a WH2 domain, alternately called a VCA domain, are activators of Arp2/3, a sevenpolypeptide complex that stimulates actin nucleation and branching (Beltzner and Pollard 2007 activity has been implicated in formation of the growth cone peripheral actin meshwork (Goldberg et al 2000). However, interference with Arp2/3 activity using a dominant-negative N-WASP WH2 domain in cultured neurons caused more rapid growth cone advance but had little apparent effect on growth cone morphology .…”

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confidence: 99%

The Arp2/3 Activators WAVE and WASP Have Distinct Genetic Interactions With Rac GTPases inCaenorhabditis elegansAxon Guidance

et al. 2008

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In the developing nervous system, axons are guided to their targets by the growth cone. Lamellipodial and filopodial protrusions from the growth cone underlie motility and guidance. Many molecules that control lamellipodia and filopodia formation, actin organization, and axon guidance have been identified, but it remains unclear how these molecules act together to control these events. Experiments are described here that indicate that, in Caenorhabditis elegans, two WH2-domain-containing activators of the Arp2/3 complex, WVE-1/WAVE and WSP-1/WASP, act redundantly in axon guidance and that GEX-2/Sra-1 and GEX-3/ Kette, molecules that control WAVE activity, might act in both pathways. WAVE activity is controlled by Rac GTPases, and data are presented here that suggest WVE-1/WAVE and CED-10/Rac act in parallel to a pathway containing WSP-1/WASP and MIG-2/RhoG. Furthermore, results here show that the CED-10/ WVE-1 and MIG-2/WSP-1 pathways act in parallel to two other molecules known to control lamellipodia and filopodia and actin organization, UNC-115/abLIM and UNC-34/Enabled. These results indicate that at least three actin-modulating pathways act in parallel to control actin dynamics and lamellipodia and filopodia formation during axon guidance (WASP-WAVE, UNC-115/abLIM, and UNC-34/Enabled). T HE growth cone of an extending axon senses and responds to extracellular guidance cues that direct axon pathfinding in the developing nervous system (Mortimer et al. 2008). Growth cone motility and guidance are mediated by the dynamic extension and retraction of lamellipodia and filopodia that are themselves the result of actin cytoskeleton-plasma membrane dynamics and interactions (Gallo and Letourneau 2004;Zhou and Cohan 2004;Pak et al. 2008). The peripheral region of the growth cone is rich in dynamic, actin-based structures including bundled microfilaments in filopodia and a lamellipodial-like meshwork of actin filaments . Multiple actin regulatory molecules are required to drive the formation of these distinct domains of actin cytoskeletal architecture in the growth cone, and the control of actin dynamics in the growth cone in response to guidance signals is an area of much interest and active study.Rac GTPases are key regulators of cytoskeletal dynamics and cellular protrusion and have been shown to control axon guidance as well as other morphogenetic events (Lundquist 2003;Watabe-Uchida et al. 2006). In Caenorhabditis elegans, the Rac GTPase CED-10 has overlapping function with the Rac-like GTPase MIG-2 in axon guidance (Lundquist et al. 2001). While MIG-2-like molecules (Mtl in Drosophila) (Hakeda-Suzuki et al. 2002) are not found in vertebrates, MIG-2 might be the C. elegans functional equivalent of vertebrate RhoG (Debakker et al. 2004). Previous work also showed that the UNC-115/abLIM actin binding protein might act downstream of Rac signaling to control lamellipodia and filopodia formation Struckhoff and Lundquist 2003;Yang and Lundquist 2005). The Enabled actin-regulatory molecule is involved in filopodi...

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Recruitment of the Arp2/3 complex and Mena for the stimulation of actin polymerization in growth cones by nerve growth factor

Cited by 33 publications

References 43 publications

Cortactin: coupling membrane dynamics to cortical actin assembly

Cortactin: coupling membrane dynamics to cortical actin assembly

Signaling mechanisms that regulate actin‐based motility processes in the nervous system

The Arp2/3 Activators WAVE and WASP Have Distinct Genetic Interactions With Rac GTPases inCaenorhabditis elegansAxon Guidance

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