scholarly journals Actin Polymerization and ESCRT Trigger Recruitment of the Fusogens Syntaxin-2 and EFF-1 to Promote Membrane Repair in C. elegans

2020 ◽  
Vol 54 (5) ◽  
pp. 624-638.e5 ◽  
Author(s):  
Xinan Meng ◽  
Qingxian Yang ◽  
Xinghai Yu ◽  
Jinghua Zhou ◽  
Xuecong Ren ◽  
...  
Keyword(s):  
Actin Polymerization ◽  
Membrane Repair ◽  
C Elegans

scholarly journals From wound response to repair – lessons from C. elegans

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Yicong Ma ◽  
Jing Xie ◽  
Chandra Sugiarto Wijaya ◽  
Suhong Xu
Keyword(s):  
Wound Repair ◽  
Actin Polymerization ◽  
Molecular Mechanisms ◽  
Model Organism ◽  
Repair Process ◽  
Tissue Level ◽  
Wound Response ◽  
Membrane Repair ◽  
General Process ◽  
C Elegans

AbstractAs a result of evolution, the ability to repair wounds allows organisms to combat environment insults. Although the general process of wound healing at the tissue level has been described for decades, the detailed molecular mechanisms regarding the early wound response and rapid wound repair at the cellular level remain little understood. Caenorhabditis elegans is a model organism widely used in the field of development, neuroscience, programmed cell death etc. The nematode skin is composed of a large epidermis associated with a transparent extracellular cuticle, which likely has a robust capacity for epidermal repair. Yet, until the last decades, relatively few studies had directly analyzed the wound response and repair process. Here we review recent findings in how C. elegans epidermis responds to wounding and initiates early actin-polymerization-based wound closure as well as later membrane repair. We also discussed some remained outstanding questions for future study.

scholarly journals Tropomyosin inhibits ADF/cofilin-dependent actin filament dynamics

2002 ◽  
Vol 156 (6) ◽  
pp. 1065-1076 ◽  
Author(s):  
Shoichiro Ono ◽  
Kanako Ono
Keyword(s):  
Actin Filament ◽  
Actin Filaments ◽  
Actin Polymerization ◽  
Biological Properties ◽  
Actin Dynamics ◽  
Background Suppression ◽  
Thin Filaments ◽  
Actin Organization ◽  
C Elegans ◽  
Filament Dynamics

Tropomyosin binds to actin filaments and is implicated in stabilization of actin cytoskeleton. We examined biochemical and cell biological properties of Caenorhabditis elegans tropomyosin (CeTM) and obtained evidence that CeTM is antagonistic to ADF/cofilin-dependent actin filament dynamics. We purified CeTM, actin, and UNC-60B (a muscle-specific ADF/cofilin isoform), all of which are derived from C. elegans, and showed that CeTM and UNC-60B bound to F-actin in a mutually exclusive manner. CeTM inhibited UNC-60B–induced actin depolymerization and enhancement of actin polymerization. Within isolated native thin filaments, actin and CeTM were detected as major components, whereas UNC-60B was present at a trace amount. Purified UNC-60B was unable to interact with the native thin filaments unless CeTM and other associated proteins were removed by high-salt extraction. Purified CeTM was sufficient to restore the resistance of the salt-extracted filaments from UNC-60B. In muscle cells, CeTM and UNC-60B were localized in different patterns. Suppression of CeTM by RNA interference resulted in disorganized actin filaments and paralyzed worms in wild-type background. However, in an ADF/cofilin mutant background, suppression of CeTM did not worsen actin organization and worm motility. These results suggest that tropomyosin is a physiological inhibitor of ADF/cofilin-dependent actin dynamics.

scholarly journals Forces drive basement membrane invasion inCaenorhabditis elegans

2018 ◽  
Vol 115 (45) ◽  
pp. 11537-11542 ◽  
Author(s):  
Rodrigo Cáceres ◽  
Nagagireesh Bojanala ◽  
Laura C. Kelley ◽  
Jes Dreier ◽  
John Manzi ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Basement Membrane ◽  
Actin Filaments ◽  
Actin Polymerization ◽  
Force Production ◽  
Developmental Event ◽  
C Elegans ◽  
Anchor Cell

During invasion, cells breach basement membrane (BM) barriers with actin-rich protrusions. It remains unclear, however, whether actin polymerization applies pushing forces to help break through BM, or whether actin filaments play a passive role as scaffolding for targeting invasive machinery. Here, using the developmental event of anchor cell (AC) invasion inCaenorhabditis elegans, we observe that the AC deforms the BM and underlying tissue just before invasion, exerting forces in the tens of nanonewtons range. Deformation is driven by actin polymerization nucleated by the Arp2/3 complex and its activators, whereas formins and cross-linkers are dispensable. Delays in invasion upon actin regulator loss are not caused by defects in AC polarity, trafficking, or secretion, as appropriate markers are correctly localized in the AC even when actin is reduced and invasion is disrupted. Overall force production emerges from this study as one of the main tools that invading cells use to promote BM disruption inC. elegans.

scholarly journals Netrin/UNC-6 triggers actin assembly and non-muscle myosin activity to drive dendrite retraction in the self-avoidance response

2018 ◽  
Author(s):  
Lakshmi Sundararajan ◽  
Cody J. Smith ◽  
Joseph D. Watson ◽  
Bryan A. Millis ◽  
Matthew J. Tyska ◽  
...  
Keyword(s):  
Avoidance Response ◽  
Actin Polymerization ◽  
The Self ◽  
Actin Assembly ◽  
Range Interaction ◽  
C Elegans ◽  
Dendrite Length ◽  
Intrinsic Mechanism ◽  
Muscle Myosin ◽  
Dendrite Retraction

SUMMARYDendrite growth is constrained by the self-avoidance response but the downstream pathways that balance these opposing mechanisms are unknown. We have proposed that the diffusible cue UNC-6(Netrin) is captured by UNC-40 (DCC) for a short-range interaction with UNC-5 to trigger self-avoidance in the C. elegans PVD neuron. Here we report that the actin-polymerizing proteins UNC-34(Ena/VASP), WSP-1(WASP), UNC-73(Trio), MIG-10(Lamellipodin) and the Arp2/3 complex effect dendrite retraction in the self-avoidance response mediated by UNC-6(Netrin). The paradoxical idea that actin polymerization results in shorter rather than longer dendrites is explained by our finding that NMY-1 (non-muscle myosin II) is necessary for retraction and could therefore mediate this effect in a contractile mechanism. Our results also show that dendrite length is determined by the antagonistic effects on the actin cytoskeleton of separate sets of effectors for retraction mediated by UNC-6(Netrin) versus outgrowth promoted by the DMA-1 receptor. Thus, our findings suggest that the dendrite length depends on an intrinsic mechanism that balances distinct modes of actin assembly for growth versus retraction.

Recruitment of Tetraspanin TSP-15 Regulates Plasma Membrane Repair in C. elegans Epidermis

2021 ◽  
Author(s):  
Qingxian Yang ◽  
Yuanyuan Wang ◽  
Xinan Meng ◽  
Chandra Sugiarto Wijaya ◽  
Xuecong Ren ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Membrane Repair ◽  
C Elegans ◽  
Plasma Membrane Repair

scholarly journals A two-step actin polymerization mechanism drives dendrite branching

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Rebecca Shi ◽  
Daniel A. Kramer ◽  
Baoyu Chen ◽  
Kang Shen
Keyword(s):  
Actin Polymerization ◽  
Molecular Mechanisms ◽  
Receptive Fields ◽  
Elongation Factor ◽  
Direct Interaction ◽  
Time Lapse ◽  
Actin Binding ◽  
Dendritic Arbor ◽  
C Elegans

Abstract Background Dendrite morphogenesis plays an essential role in establishing the connectivity and receptive fields of neurons during the development of the nervous system. To generate the diverse morphologies of branched dendrites, neurons use external cues and cell surface receptors to coordinate intracellular cytoskeletal organization; however, the molecular mechanisms of how this signaling forms branched dendrites are not fully understood. Methods We performed in vivo time-lapse imaging of the PVD neuron in C. elegans in several mutants of actin regulatory proteins, such as the WAVE Regulatory Complex (WRC) and UNC-34 (homolog of Enabled/Vasodilator-stimulated phosphoprotein (Ena/VASP)). We examined the direct interaction between the WRC and UNC-34 and analyzed the localization of UNC-34 in vivo using transgenic worms expressing UNC-34 fused to GFP. Results We identify a stereotyped sequence of morphological events during dendrite outgrowth in the PVD neuron in C. elegans. Specifically, local increases in width (“swellings”) give rise to filopodia to facilitate a “rapid growth and pause” mode of growth. In unc-34 mutants, filopodia fail to form but swellings are intact. In WRC mutants, dendrite growth is largely absent, resulting from a lack of both swelling and filopodia formation. We also found that UNC-34 can directly bind to the WRC. Disrupting this binding by deleting the UNC-34 EVH1 domain prevented UNC-34 from localizing to swellings and dendrite tips, resulting in a stunted dendritic arbor and reduced filopodia outgrowth. Conclusions We propose that regulators of branched and linear F-actin cooperate to establish dendritic branches. By combining our work with existing literature, we propose that the dendrite guidance receptor DMA-1 recruits the WRC, which polymerizes branched F-actin to generate “swellings” on a mother dendrite. Then, WRC recruits the actin elongation factor UNC-34/Ena/VASP to initiate growth of a new dendritic branch from the swelling, with the help of the actin-binding protein UNC-115/abLIM. Extension of existing dendrites also proceeds via swelling formation at the dendrite tip followed by UNC-34-mediated outgrowth. Following dendrite initiation and extension, the stabilization of branches by guidance receptors further recruits WRC, resulting in an iterative process to build a complex dendritic arbor.

scholarly journals WTS-1/LATS regulates endocytic recycling by restraining F-actin assembly in a synergistic manner

2021 ◽  
Author(s):  
Hanchong Zhang ◽  
Zihang Cheng ◽  
Wenbo Li ◽  
Jie Hu ◽  
Linyue Zhao ◽  
...  
Keyword(s):  
Actin Polymerization ◽  
Hippo Pathway ◽  
Actin Assembly ◽  
Core Component ◽  
Endocytic Recycling ◽  
Actin Organization ◽  
C Elegans ◽  
The Hippo Pathway ◽  
Homeostatic Mechanisms

The disruption of endosomal actin architecture negatively affects endocytic recycling. However, the underlying homeostatic mechanisms that regulate actin organization during recycling remain unclear. In this study, we identified a synergistic endosomal actin assembly restricting mechanism in C. elegans involving WTS-1/LATS kinase, which is a core component of the Hippo pathway. WTS-1 resides on the sorting endosomes and colocalizes with the actin polymerization regulator PTRN-1/CAMSAPs. We observed an increase in PTRN-1-labeled structures in WTS-1-deficient cells, indicating that WTS-1 can limit the endosomal localization of PTRN-1. Accordingly, the actin overaccumulation phenotype in WTS-1-depleted cells was mitigated by the associated PTRN-1 loss. We further demonstrated that recycling defects and actin overaccumulation in WTS-1-deficient cells were reduced by the overexpression of constitutively active UNC-60A/cofilin(S3A), which aligns with the role of LATS as a positive regulator of cofilin activity. Altogether, our data confirmed previous findings, and we proposed an additional model: WTS-1 acts alongside the UNC-60A/cofilin-mediated actin disassembly to restrict the assembly of endosomal F-actin by curbing PTRN-1 dwelling on endosomes, preserving recycling transport.

scholarly journals The Role of Glycosyltransferases in Colorectal Cancer

2021 ◽  
Vol 22 (11) ◽  
pp. 5822
Author(s):  
Cecilia Fernández-Ponce ◽  
Noelia Geribaldi-Doldán ◽  
Ismael Sánchez-Gomar ◽  
Roberto Navarro Quiroz ◽  
Linda Atencio Ibarra ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Actin Polymerization ◽  
Transforming Growth Factor ◽  
Cell Function ◽  
Cell Polarization ◽  
Mucosal Barrier ◽  
Membrane Repair

Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Post-translational modifications (PTMs) have been extensively studied in malignancies due to its relevance in tumor pathogenesis and therapy. This review is focused on the dysregulation of glycosyltransferase expression in CRC and its impact in cell function and in several biological pathways associated with CRC pathogenesis, prognosis and therapeutic approaches. Glycan structures act as interface molecules between cells and their environment and in several cases facilitate molecule function. CRC tissue shows alterations in glycan structures decorating molecules, such as annexin-1, mucins, heat shock protein 90 (Hsp90), β1 integrin, carcinoembryonic antigen (CEA), epidermal growth factor receptor (EGFR), insulin-like growth factor-binding protein 3 (IGFBP3), transforming growth factor beta (TGF-β) receptors, Fas (CD95), PD-L1, decorin, sorbin and SH3 domain-containing protein 1 (SORBS1), CD147 and glycosphingolipids. All of these are described as key molecules in oncogenesis and metastasis. Therefore, glycosylation in CRC can affect cell migration, cell–cell adhesion, actin polymerization, mitosis, cell membrane repair, apoptosis, cell differentiation, stemness regulation, intestinal mucosal barrier integrity, immune system regulation, T cell polarization and gut microbiota composition; all such functions are associated with the prognosis and evolution of the disease. According to these findings, multiple strategies have been evaluated to alter oligosaccharide processing and to modify glycoconjugate structures in order to control CRC progression and prevent metastasis. Additionally, immunotherapy approaches have contemplated the use of neo-antigens, generated by altered glycosylation, as targets for tumor-specific T cells or engineered CAR (Chimeric antigen receptors) T cells.

scholarly journals Spectrin-based Membrane Mechanics Is Asymmetric and Remodels during Neural Development

2020 ◽  
Author(s):  
Ru Jia ◽  
Yongping Chai ◽  
Chao Xie ◽  
Gai Liu ◽  
Zhiwen Zhu ◽  
...  
Keyword(s):  
Neural Development ◽  
Actin Polymerization ◽  
Structural Integrity ◽  
Leading Edge ◽  
Membrane Skeleton ◽  
Membrane Mechanics ◽  
Dendrite Morphology ◽  
C Elegans ◽  
Dendrite Formation ◽  
Neuroblast Migration

AbstractPerturbation of spectrin-based membrane mechanics causes hereditary elliptocytosis and spinocerebellar ataxia, but the underlying cellular basis of pathogenesis remains unclear. Here, we introduced the conserved disease-associated spectrin mutations into the C. elegans genome and studied the contribution of spectrin to neuronal migration and dendrite formation in developing larvae. The loss of spectrin generates an ectopic actin polymerization outside of the existing front and secondary membrane protrusions, leading to defective neuronal positioning and dendrite morphology in adult animals. Spectrin accumulates in the lateral and the rear of migrating neuroblasts and redistributes from the soma into the newly formed dendrites, indicating that the spectrin-based membrane skeleton is asymmetric and remodels to regulate actin assembly and cell shape during development. We affinity-purified spectrin from C. elegans and showed that its binding partner ankyrin functions with spectrin. Asymmetry and remodeling of membrane skeleton may enable spatiotemporal modulation of membrane mechanics for distinct developmental events.Significance StatementThe biomechanical regulation of neural development is largely unknown. The spectrin-based membrane skeleton is essential for the structural integrity of the plasma membrane. This study addresses the function and behavior of spectrin in neuroblast migration and dendrite formation. The loss of spectrin generates an ectopic actin polymerization outside of the existing front, leading to defective neuronal positioning and dendrite morphology. Spectrin is absent from the leading edge but accumulates in the posterior of migrating neuroblasts and redistributes from the soma into the nascent dendrites, indicating that the membrane skeleton is asymmetric and remodels. Asymmetry and remodeling of the membrane skeleton may enable spatiotemporal modulation of membrane mechanics for distinct developmental events.

The glycomes of Caenorhabditis elegans and other model organisms

2002 ◽  
Vol 69 ◽  
pp. 117-134 ◽  
Author(s):  
Stuart M. Haslam ◽  
David Gems ◽  
Howard R. Morris ◽  
Anne Dell
Keyword(s):  
Caenorhabditis Elegans ◽  
Current Knowledge ◽  
Structural Data ◽  
Model Organisms ◽  
Entire Genome ◽  
C Elegans ◽  
The Face ◽  
Area Of Concern ◽  
Nematode Worm

There is no doubt that the immense amount of information that is being generated by the initial sequencing and secondary interrogation of various genomes will change the face of glycobiological research. However, a major area of concern is that detailed structural knowledge of the ultimate products of genes that are identified as being involved in glycoconjugate biosynthesis is still limited. This is illustrated clearly by the nematode worm Caenorhabditis elegans, which was the first multicellular organism to have its entire genome sequenced. To date, only limited structural data on the glycosylated molecules of this organism have been reported. Our laboratory is addressing this problem by performing detailed MS structural characterization of the N-linked glycans of C. elegans; high-mannose structures dominate, with only minor amounts of complex-type structures. Novel, highly fucosylated truncated structures are also present which are difucosylated on the proximal N-acetylglucosamine of the chitobiose core as well as containing unusual Fucα1–2Gal1–2Man as peripheral structures. The implications of these results in terms of the identification of ligands for genomically predicted lectins and potential glycosyltransferases are discussed in this chapter. Current knowledge on the glycomes of other model organisms such as Dictyostelium discoideum, Saccharomyces cerevisiae and Drosophila melanogaster is also discussed briefly.

Sign in / Sign up

Export Citation Format

Share Document