Regulation of actin dynamics by WASP and WAVE family proteins

Stradal, Theresia E. B.; Rottner, Klemens; Disanza, Andrea; Confalonieri, Stefano; Innocenti, Metello; Scita, Giorgio

doi:10.1016/j.tcb.2004.04.007

Cited by 266 publications

(256 citation statements)

References 82 publications

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“…Consistent with this finding, is the fact that the de novo Arp2/3-dependent actin filament elongation, mediated by the WAVE family of proteins, is essential for the formation of dorsal membrane extensions needed to engulf fluids Innocenti et al, 2005). This pathway is under the control of the RhoGTPase, RAC, which mediates actin remodeling at the plasma membrane (PM) by controlling WASP family VE rprolin-homologous proteins (WAVEs) (Stradal et al, 2004). However, the sole activation of RAC is apparently insufficient to induce circular ruffles, underscoring the need for additional and coordinated signaling cascades (Lanzetti et al, 2004).…”

Section: Introductionmentioning

confidence: 73%

The Primate-specific Protein TBC1D3 Is Required for Optimal Macropinocytosis in a Novel ARF6-dependent Pathway

Frittoli

Palamidessi

Pizzigoni

et al. 2008

MBoC

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The generation of novel genes and proteins throughout evolution has been proposed to occur as a result of whole genome and gene duplications, exon shuffling, and retrotransposition events. The analysis of such genes might thus shed light into the functional complexity associated with highly evolved species. One such case is represented by TBC1D3, a primatespecific gene, harboring a TBC domain. Because TBC domains encode Rab-specific GAP activities, TBC-containing proteins are predicted to play a major role in endocytosis and intracellular traffic. Here, we show that the TBC1D3 gene originated late in evolution, likely through a duplication of the RNTRE locus, and underwent gene amplification during primate speciation. Despite possessing a TBC domain, TBC1D3 is apparently devoid of Rab-GAP activity. However, TBC1D3 regulates the optimal rate of epidermal growth factor-mediated macropinocytosis by participating in a novel pathway involving ARF6 and RAB5. In addition, TBC1D3 binds and colocalize to GGA3, an ARF6-effector, in an ARF6-dependent manner, and synergize with it in promoting macropinocytosis, suggesting that the two proteins act together in this process. Accordingly, GGA3 siRNA-mediated ablation impaired TBC1D3-induced macropinocytosis. We thus uncover a novel signaling pathway that appeared after primate speciation. Within this pathway, a TBC1D3:GGA3 complex contributes to optimal propagation of signals, ultimately facilitating the macropinocytic process. INTRODUCTIONGene duplication, exon shuffling, and retrotransposition events played crucial roles during vertebrate evolution (Long, 2001;McLysaght et al., 2002;Brosius, 2003). About 5% of the human genome is composed of duplicated segments that emerged during the past 35 million years of primate evolution, resulting in the generation of novel protein functions (Courseaux and Nahon, 2001;Taylor and Raes, 2004).One of the cellular processes, whose regulation has became more and more complex and tightly regulated during evolution is endocytosis. Endocytosis serves to maintain cellular and organismal homeostasis by mediating the uptake of fluids, solutes, and signaling molecules and their receptors. Multiple mechanisms of endocytosis operate within a single cell (Conner and Schmid, 2003). Among them, two major categories are phagocytosis and pinocytosis, which mediate the uptake of particles or of fluid, respectively (Conner and Schmid, 2003).Pinocytosis encompasses a variety of different membraneentry routes and is invariably characterized by the relatively small size (50 -150 nm) of the internalized particles. Large volumes of fluid are, instead, engulfed by extension, folding, and closure of plasma membranes (PM) through a process termed macropinocytosis (Swanson and Watts, 1995). Macropinocytosis displays many similarities to phagocytosis; the biochemical and cellular components of these endocytic mechanisms have been best characterized in hematopoietic cells, in processes such as phagocytosis by macrophages in response to Fc receptor stimulation, or ma...

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Section: Introductionmentioning

confidence: 73%

The Primate-specific Protein TBC1D3 Is Required for Optimal Macropinocytosis in a Novel ARF6-dependent Pathway

Frittoli

Palamidessi

Pizzigoni

et al. 2008

MBoC

Self Cite

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“…WAVE proteins are intrinsically inactive and exist in a pentameric complex known as the WAVE regulatory complex (WRC), which includes ABI1 or ABI2, NAP1 (also known as NCKAP1) or NCKAP1L, CYFIP1 or CYFIP2 and HSPC300 (Chen et al, 2010;Eden et al, 2002;Ismail et al, 2009;Stradal et al, 2004) (see poster). Rac1 has been shown to activate WAVE proteins through an interaction with the WRC component CYFIP1/ 2 (Chen et al, 2010).…”

Section: Jmymentioning

confidence: 99%

Cellular functions of WASP family proteins at a glance

Alekhina

Burstein

Billadeau

2017

Journal of Cell Science

158

172

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Proteins of the Wiskott–Aldrich syndrome protein (WASP) family function as nucleation-promoting factors for the ubiquitously expressed Arp2/3 complex, which drives the generation of branched actin filaments. Arp2/3-generated actin regulates diverse cellular processes, including the formation of lamellipodia and filopodia, endocytosis and/or phagocytosis at the plasma membrane, and the generation of cargo-laden vesicles from organelles including the Golgi, endoplasmic reticulum (ER) and the endo-lysosomal network. Recent studies have also identified roles for WASP family members in promoting actin dynamics at the centrosome, influencing nuclear shape and membrane remodeling events leading to the generation of autophagosomes. Interestingly, several WASP family members have also been observed in the nucleus where they directly influence gene expression by serving as molecular platforms for the assembly of epigenetic and transcriptional machinery. In this Cell Science at a Glance article and accompanying poster, we provide an update on the subcellular roles of WHAMM, JMY and WASH (also known as WASHC1), as well as their mechanisms of regulation and emerging functions within the cell.

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“…The VCA domain of SCAR/WAVE proteins acts to activate the Arp2/3 complex, and consequently, increases the actin filament nucleation and branching activities of the complex (Stradal et al, 2004). Sequence Figure 6.…”

Section: Tut1 Encodes a Functional Scar/wave Proteinmentioning

confidence: 99%

Rice TUTOU1 Encodes a Suppressor of cAMP Receptor-Like Protein That Is Important for Actin Organization and Panicle Development

et al. 2015

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Panicle development, a key event in rice (Oryza sativa) reproduction and a critical determinant of grain yield, forms a branched structure containing multiple spikelets. Genetic and environmental factors can perturb panicle development, causing panicles to degenerate and producing characteristic whitish, small spikelets with severely reduced fertility and yield; however, little is known about the molecular basis of the formation of degenerating panicles in rice. Here, we report the identification and characterization of the rice panicle degenerative mutant tutou1 (tut1), which shows severe defects in panicle development. The tut1 also shows a pleiotropic phenotype, characterized by short roots, reduced plant height, and abnormal development of anthers and pollen grains. Molecular genetic studies revealed that TUT1 encodes a suppressor of cAMP receptor/Wiskott-Aldrich syndrome protein family verprolin-homologous (SCAR/WAVE)-like protein. We found that TUT1 contains conserved functional domains found in eukaryotic SCAR/WAVE proteins, and was able to activate Actin-related protein2/3 to promote actin nucleation and polymerization in vitro. Consistently, tut1 mutants show defects in the arrangement of actin filaments in trichome. These results indicate that TUT1 is a functional SCAR/WAVE protein and plays an important role in panicle development.

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Regulation of actin dynamics by WASP and WAVE family proteins

Cited by 266 publications

References 82 publications

The Primate-specific Protein TBC1D3 Is Required for Optimal Macropinocytosis in a Novel ARF6-dependent Pathway

The Primate-specific Protein TBC1D3 Is Required for Optimal Macropinocytosis in a Novel ARF6-dependent Pathway

Cellular functions of WASP family proteins at a glance

Rice TUTOU1 Encodes a Suppressor of cAMP Receptor-Like Protein That Is Important for Actin Organization and Panicle Development

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