Regulation of actin assembly by SCAR/WAVE proteins

Ibarra, Neysi; Pollitt, Alice Y.; Insall, Robert H.

doi:10.1042/bst0331243

Cited by 63 publications

(38 citation statements)

References 38 publications

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“…Here, actin assembly and lateral branching (dendritic nucleation) are mainly controlled by the Arp2/3 complex, a seven subunit protein and major initiator of actin assembly. The activity of the Arp2/3 complex itself is controlled by actin nucleation-promoting factors, such as the N-WASP or the Scar/WAVE complexes which are themselves recruited to and activated at the membrane by Rac1 [172][173][174]. Increased expression of Arp2/3 and WAVE2 has been shown to correlate with poor prognosis in breast and liver carcinomas underlining the relevance of lamellipodia-like structures in cancer progression [175,176].…”

Section: Lamellipodia and Filopodiamentioning

confidence: 99%

EMT, the cytoskeleton, and cancer cell invasion

Yilmaz

Christofori

2009

Cancer Metastasis Rev

1,528

1,345

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The metastatic process, i.e. the dissemination of cancer cells throughout the body to seed secondary tumors at distant sites, requires cancer cells to leave the primary tumor and to acquire migratory and invasive capabilities. In a process of epithelial-mesenchymal transition (EMT), besides changing their adhesive repertoire, cancer cells employ developmental processes to gain migratory and invasive properties that involve a dramatic reorganization of the actin cytoskeleton and the concomitant formation of membrane protrusions required for invasive growth. The molecular processes underlying such cellular changes are still only poorly understood, and the various migratory organelles, including lamellipodia, filopodia, invadopodia and podosomes, still require a better functional and molecular characterization. Notably, direct experimental evidence linking the formation of migratory membrane protrusions and the process of EMT and tumor metastasis is still lacking. In this review, we have summarized recent novel insights into the molecular processes and players underlying EMT on one side and the formation of invasive membrane protrusions on the other side.

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Section: Lamellipodia and Filopodiamentioning

confidence: 99%

EMT, the cytoskeleton, and cancer cell invasion

Yilmaz

Christofori

2009

Cancer Metastasis Rev

1,528

1,345

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“…Nap1 is a member of a conserved complex with Sra-1 (also known as CYFIP), Abi1 and HSPC300 that serves to regulate SCAR/WAVE activity. SCAR/WAVE then regulates Arp2/3-dependent actin polymerization (Ibarra et al, 2005;Machesky and Insall, 1998;Smith and Li, 2004;Vartiainen and Machesky, 2004). Positive regulation of SCAR/WAVE by Kette/Nap1 has been shown to be essential for proper SCAR/WAVE localization and myoblast fusion in Drosophila (Richardson et al, 2007).…”

Section: Pharmacological Inhibition Of Actin-cytoskeletal Remodeling mentioning

confidence: 99%

Nap1-mediated actin remodeling is essential for mammalian myoblast fusion

Nowak

Nahirney

Hadjantonakis

et al. 2009

Journal of Cell Science

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Myoblast fusion is crucial for the formation, growth, maintenance and regeneration of healthy skeletal muscle. Unfortunately, the molecular machinery, cell behaviors, and membrane and cytoskeletal remodeling events that govern fusion and myofiber formation remain poorly understood. Using time-lapse imaging approaches on mouse C2C12 myoblasts, we identify discrete and specific molecular events at myoblast membranes during fusion and myotube formation. These events include rearrangement of cell shape from fibroblast to spindle-like morphologies, changes in lamellipodial and filopodial extensions during different periods of differentiation, and changes in membrane alignment and organization during fusion. We find that actin-cytoskeleton remodeling is crucial for these events: pharmacological inhibition of F-actin polymerization leads to decreased lamellipodial and filopodial extensions and to reduced myoblast fusion. Additionally, shRNA-mediated inhibition of Nap1, a member of the WAVE actin-remodeling complex, results in accumulations of F-actin structures at the plasma membrane that are concomitant with a decrease in myoblast fusion. Our data highlight distinct and essential roles for actin cytoskeleton remodeling during mammalian myoblast fusion, provide a platform for cellular and molecular dissection of the fusion process, and suggest a functional conservation of Nap1-regulated actin-cytoskeleton remodeling during myoblast fusion between mammals and Drosophila.Supplementary material available online at

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“…Potential regulators of ARP2/3 include the ABI proteins, initially discovered to function as downstream targets of ABL non-receptor tyrosine kinases implicated in RAC-dependent cytoskeletal organization and remodeling (Courtney et al, 2000;Funato et al, 2004;Jenei et al, 2005;Stradal et al, 2001), in addition to processes such as cell migration, neuronal development, growth cone pathfinding and endocytosis (Courtney et al, 2000;Grove et al, 2004;Ibarra et al, 2005;So et al, 2000). ABI family members localize to the actin-rich tips of lamellipodia and filopodia, and are widely expressed in the developing murine nervous system (Courtney et al, 2000;Stradal et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

The cell migration molecule UNC-53/NAV2 is linked to the ARP2/3 complex by ABI-1

et al. 2009

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The shape changes that are required to position a cell to migrate or grow out in a particular direction involve a coordinated reorganization of the actin cytoskeleton. Although it is known that the ARP2/3 complex nucleates actin filament assembly, exactly how the information from guidance cues is integrated to elicit ARP2/3-mediated remodeling during outgrowth remains vague. Previous studies have shown that C. elegans UNC-53 and its vertebrate homolog NAV (Neuronal Navigators) are required for the migration of cells and neuronal processes. We have identified ABI-1 as a novel molecular partner of UNC-53/NAV2 and have found that a restricted calponin homology (CH) domain of UNC-53 is sufficient to bind ABI-1. ABI-1 and UNC-53 have an overlapping expression pattern, and display similar cell migration phenotypes in the excretory cell, and in mechanosensory and motoneurons. Migration defects were also observed after RNAi of proteins known to function with abi-1 in actin dynamics, including nck-1, wve-1 and arx-2. We propose that UNC-53/NAV2, through its CH domain, acts as a scaffold that links ABI-1 to the ARP2/3 complex to regulate actin cytoskeleton remodeling.

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Regulation of actin assembly by SCAR/WAVE proteins

Cited by 63 publications

References 38 publications

EMT, the cytoskeleton, and cancer cell invasion

EMT, the cytoskeleton, and cancer cell invasion

Nap1-mediated actin remodeling is essential for mammalian myoblast fusion

The cell migration molecule UNC-53/NAV2 is linked to the ARP2/3 complex by ABI-1

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