Essential role of the<i>C. elegans</i>Arp2/3 complex in cell migration during ventral enclosure

Sawa, Mariko; Suetsugu, Shiro; Sugimoto, Akihiro; Miki, Hiroaki; Yamamoto, Masayuki; Takenawa, Tadaomi

doi:10.1242/jcs.00362

Cited by 114 publications

(103 citation statements)

References 57 publications

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“…We report here that three actin-remodeling proteins (Sawa et al 2003). Considering our results with the properly migrated CAN cells in wild-type, wsp-1, wve-1 RNAi, evidence presented by Sawa et al (2003), we conclude unc-34(e315), wsp-1 RNAi;unc-34(e315), and wve-1 RNAi; uncthat wsp-1 plays a role in ventral cleft closure during 34(e315) animals.…”

Section: A C Elegans N-wasp Homolog Can Compensate For Asupporting

confidence: 82%

Caenorhabditis elegans WASP and Ena/VASP Proteins Play Compensatory Roles in Morphogenesis and Neuronal Cell Migration

et al. 2004

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We report here that WASP and Ena/VASP family proteins play overlapping roles in C. elegans morphogenesis and neuronal cell migration. Specifically, these studies demonstrate that UNC-34/Ena plays a role in morphogenesis that is revealed only in the absence of WSP-1 function and that WSP-1 has a role in neuronal cell migration that is revealed only in the absence of UNC-34/Ena activity. To identify additional genes that act in parallel to unc-34/ena during morphogenesis, we performed a screen for synthetic lethals in an unc-34 null mutant background utilizing an RNAi feeding approach. To our knowledge, this is the first reported RNAi-based screen for genetic interactors. As a result of this screen, we identified a second C. elegans WASP family protein, wve-1, that is most homologous to SCAR/WAVE proteins. Animals with impaired wve-1 function display defects in gastrulation, fail to undergo proper morphogenesis, and exhibit defects in neuronal cell migrations and axon outgrowth. Reducing wve-1 levels in either unc-34/ena or wsp-1 mutant backgrounds also leads to a significant enhancement of the gastrulation and morphogenesis defects. Thus, unc-34/ena, wsp-1, and wve-1 play overlapping roles during embryogenesis and unc-34/ena and wsp-1 play overlapping roles in neuronal cell migration. These observations show that WASP and Ena/VASP proteins can compensate for each other in vivo and provide the first demonstration of a role for Ena/VASP proteins in gastrulation and morphogenesis. In addition, our results provide the first example of an in vivo role for WASP family proteins in neuronal cell migrations and cytokinesis in metazoans. D RAMATIC and often rapid changes in filamentous binds the consensus motif (D/E)-FFPPPP-X(D/E)(D/E) actin (F-actin) abundance and distribution are esand is sufficient to target Ena/VASP proteins to focal sential for a range of cellular processes, including cell adhesions and to Listeria (Gertler et al. 1996; Niebuhr polarity, vesicular trafficking, cytokinesis, and cellular et al. 1997; Ahern-Djamali et al. 1998). The central PRD movements (Carlier et al. 2003). A large number of binds several known SH3-domain-containing proteins as activities that regulate F-actin abundance and distribuwell as the actin exchange factor profilin (Gertler et al. tion have been described and many of them attributed Reinhard et al. 1995). Finally, the C-terminal to proteins that are evolutionarily conserved. Although EVH2 domain binds globular and F-actin and is required many of these activities are well characterized in vitro, for multimerization (Bachmann et al. 1999). Previous their exact role in vivo is still unclear in many instances.work in fibroblast cells in vitro supports a model where The Ena/VASP proteins constitute a family of evoluEna/VASP proteins promote F-actin elongation by bindtionarily conserved actin-regulating proteins that act in ing free filament ends and by inhibiting the activity of many cellular processes, including axon guidance, phagocapping proteins that prevent filament...

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Section: A C Elegans N-wasp Homolog Can Compensate For Asupporting

confidence: 82%

Caenorhabditis elegans WASP and Ena/VASP Proteins Play Compensatory Roles in Morphogenesis and Neuronal Cell Migration

et al. 2004

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“…Mutations in key components of the SCAR/ WAVE-Arp2/3 complex result in various defects in yeast and animals (Winter et al, 1999;Di Nardo et al, 2005). In many cases, these mutations cause embryonic arrest and zygotic lethality by impairing various cellular activities (Severson et al, 2002;Sawa et al, 2003;Vartiainen and Machesky, 2004). However, in Arabidopsis and maize, mutations in the SCAR/WAVE complex genes cause relatively weak phenotypes, affecting cell morphogenesis and development of the trichome and the hypocotyl (Frank and Smith, 2002;Uhrig et al, 2007).…”

Section: Discussionmentioning

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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“…Following elimination of all genes previously shown to cause developmental delay or sterility 41 , we identified 61 genes whose knockdown reproducibly resulted in decreased AO staining (Figure 3e , Supplementary Table S1). In addition to the known genes required for corpse recognition (ced-1) and internalization (ced-5 and ced-6) present in the RNAi library 50 , we also identified components of the Arp2/3 complex in C. elegans, arx-3 and arx-5 51 . Since the Arp2/3 complex plays a key role during actin reorganization and corpse removal in mammalian systems 52 , the inactivation of the Arp2/3 complex in C. elegans may similarly interfere with actin-dependent corpse internalization.…”

Section: An Unbiased Genetic Screen Identifies Additional Genes Requimentioning

confidence: 99%

A pathway for phagosome maturation during engulfment of apoptotic cells

et al. 2008

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The efficient removal of apoptotic cells is critical for the physiological well-being of the organism 1 Ã 4 ; defects in corpse removal have been linked to autoimmune disease 4,5 . While several players regulating the early steps of corpse recognition and internalization have been characterized 6 , the molecules and mechanisms relevant to the subsequent processing of the internalized corpses are poorly understood. Here, we identify a novel pathway for the processing of internalized apoptotic cells in C. elegans and in mammals. First, we show that RAB-5 and RAB-7 are sequentially recruited to phagosomes containing apoptotic corpses as they mature within phagocytes, and that both proteins are required for efficient corpse clearance. We then used targeted genetic screens to identify players regulating the recruitment and/or retention of Rab5 and Rab7 to phagosomes. Seven members of the HOPS complex (a Rab7 activator/effector complex) were required for Rab7 localization or retention on phagosomes. In an effort to identify factors that regulate Rab5 recruitment, we undertook an unbiased reverse genetic screen and identified 61 genes potentially required for corpse removal. In-depth analysis of two candidate genes, vps-34 and dyn-1/ dynamin, showed accumulation of internalized, but undegraded corpses within abnormal phagosomes that are defective in RAB-5 recruitment. Using a series of genetic and biochemical experiments in worms and mammalian cells, we ordered these proteins in a pathway, with DYN-1 functioning upstream of VPS-34, in the recruitment/retention of Rab5 to the nascent phagosome. Further, we identified a novel biochemical complex containing Vps34, dynamin and Rab5 GDP , providing a mechanism for Rab5 recruitment to the nascent phagosome.Removal of apoptotic cells (engulfment) is an essential process that occurs throughout life in multi-cellular animals as part of development, homeostasis, and wound healing1Ã4 , 7 , 8. Engulfment) can be broken down into a series of steps, comprising recognition, internalization, phagosome maturation and finally lysosomal degradation of the apoptotic cell by the phagocyte. In mammals, impaired clearance of apoptotic cell corpses can lead to exposure of autoantigens, resulting in onset of autoimmune diseases, such as systemic lupus erythematosus 4,9,10 . Modulation of the engulfment process is therefore a potential therapeutic target in these conditions. One of the fundamental challenges in understanding how defects in engulfment of apoptotic cells translates into diseased states is the identification of critical players involved in corpse removal and how these proteins orchestrate the different stages of engulfment.The nematode C. elegans represents a powerful genetic tool for the study of programmed cell death 11,12 . Large numbers of cells are induced to die during two periods in the life of a worm: during embryonic and larval morphogenesis and during germ cell development 13 . Genetic studies have identified two evolutionarily conserved signaling pathways invol...

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Essential role of theC. elegansArp2/3 complex in cell migration during ventral enclosure

Cited by 114 publications

References 57 publications

Caenorhabditis elegans WASP and Ena/VASP Proteins Play Compensatory Roles in Morphogenesis and Neuronal Cell Migration

Caenorhabditis elegans WASP and Ena/VASP Proteins Play Compensatory Roles in Morphogenesis and Neuronal Cell Migration

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

A pathway for phagosome maturation during engulfment of apoptotic cells

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