The novel intestinal filament organizer IFO-1 contributes to epithelial integrity in concert with ERM-1 and DLG-1

Carberry, Katrin; Wiesenfahrt, Tobias; Geisler, Florian; Stöcker, Stephanie; Gerhardus, Harald; Überbach, Daniel; Davis, Wayne M.; Jørgensen, Erik M.; Leube, Rudolf E.; Bossinger, Olaf

doi:10.1242/jcs.112854

Cited by 5 publications

(18 citation statements)

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“…Knockdown or knockout of the genes coding for these proteins might thus potentially phenocopy CCL2 toxicity. Even though knockdown or knockout of act-5 , eps-8 , erm-1 , and several intermediate filaments do affect brush border and terminal web structures [ 27 , 30 , 49 – 51 ], none of their phenotypes at the fluorescence or TEM microscopy level was similar to what we observed with CCL2, with the exception of knockdown of act-5 , which can induce terminal web gaps [ 19 ]. However, knockdown of act-5 on PGP-1::GFP expressing worms only partially reproduced the plasma membrane changes observed following CCL2 treatment ( S5 Fig and Fig 4A ).…”

Section: Discussionmentioning

confidence: 54%

“…elegans L4 larvae were analyzed using transmission electron microscopy (TEM) ( Fig 3 ). Control animals showed the typical intestinal brush border morphology ( S1B Fig ) consisting of a dense brush border of microvilli ( Fig 3A , asterisk) surrounded by a glycocalyx ( Fig 3C , arrow) and stabilized by the terminal web, a network of actin and intermediate filaments running below and in parallel to the apical plasma membrane ([ 27 ]; Fig 3C , arrowhead). By contrast, in animals fed 24 h on CCL2-expressing E .…”

Section: Resultsmentioning

confidence: 99%

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Disruption of the C. elegans Intestinal Brush Border by the Fungal Lectin CCL2 Phenocopies Dietary Lectin Toxicity in Mammals

et al. 2015

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Lectins are non-immunoglobulin carbohydrate-binding proteins without enzymatic activity towards the bound carbohydrates. Many lectins of e.g. plants or fungi have been suggested to act as toxins to defend the host against predators and parasites. We have previously shown that the Coprinopsis cinerea lectin 2 (CCL2), which binds to α1,3-fucosylated N-glycan cores, is toxic to Caenorhabditis elegans and results in developmental delay and premature death. In this study, we investigated the underlying toxicity phenotype at the cellular level by electron and confocal microscopy. We found that CCL2 directly binds to the intestinal apical surface and leads to a highly damaged brush border with loss of microvilli, actin filament depolymerization, and invaginations of the intestinal apical plasma membrane through gaps in the terminal web. We excluded several possible toxicity mechanisms such as internalization and pore-formation, suggesting that CCL2 acts directly on intestinal apical plasma membrane or glycocalyx proteins. A genetic screen for C. elegans mutants resistant to CCL2 generated over a dozen new alleles in bre 1, ger 1, and fut 1, three genes required for the synthesis of the sugar moiety recognized by CCL2. CCL2-induced intestinal brush border defects in C. elegans are similar to the damage observed previously in rats after feeding the dietary lectins wheat germ agglutinin or concanavalin A. The evolutionary conserved reaction of the brush border between mammals and nematodes might allow C. elegans to be exploited as model organism for the study of dietary lectin-induced intestinal pathology in mammals.

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Section: Discussionmentioning

confidence: 54%

Section: Resultsmentioning

confidence: 99%

Disruption of the C. elegans Intestinal Brush Border by the Fungal Lectin CCL2 Phenocopies Dietary Lectin Toxicity in Mammals

et al. 2015

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“…Specific topological cues and/or transport machineries are obviously necessary to support the establishment of these different types of IF network arrangements. Furthermore, mechanisms must be in place to maintain these specialized distribution patterns (e.g., see Iwatsuki andSuda 2010 andCarberry et al 2012 for polarized epithelial cells).…”

Section: If Motility Is Needed For Cell Type-and Function-dependent Fmentioning

confidence: 99%

Intracellular Motility of Intermediate Filaments

Leube

Moch

Windoffer

2017

Cold Spring Harb Perspect Biol

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SUMMARYThe establishment and continuous cell type-specific adaptation of cytoplasmic intermediate filament (IF) networks are linked to various types of IF motility. Motor protein-driven active transport, linkage to other cellular structures, diffusion of small soluble subunits, and intrinsic network elasticity all contribute to the motile behavior of IFs. These processes are subject to regulation by multiple signaling pathways. IF motility is thereby connected to and involved in many basic cellular processes guarding the maintenance of cell and tissue integrity. Disturbances of IF motility are linked to diseases that are characterized by cytoplasmic aggregates containing IF proteins together with other cellular components.

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“…Indeed, intestinal IF networks have essential roles in epithelial polarization, maintenance of lumen morphology, and protection from environmental stresses (Etienne-Manneville, 2018; Salas et al, 2016;Sanghvi-Shah and Weber, 2017;Toivola et al, 2010). In the C. elegans intestine, loss of IF subunits, or of the intermediate filament organizers IFO-1 and SMA-5, can result in morphological abnormalities of the lumen and increased susceptibility to microbial, osmotic, and oxidative stresses (Carberry et al, 2012;Geisler et al, , 2019Geisler et al, , 2020.…”

Section: Introductionmentioning

confidence: 99%

BBLN-1 is essential for intermediate filament organization and apical membrane morphology

Remmelzwaal

Geisler

Stucchi

et al. 2020

Preprint

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Epithelial tubes are essential components of metazoan organ systems that control the flow of fluids and the exchange of materials between body compartments and the outside environment. The size and shape of the central lumen confer important characteristics to tubular organs and need to be carefully controlled. Here, we identify the small coiled-coil protein BBLN-1 as a regulator of lumen morphology in the C. elegans intestine. Loss of BBLN-1 causes the formation of bubble-shaped invaginations of the apical membrane into the cytoplasm of intestinal cells, and abnormal aggregation of the subapical intermediate filament (IF) network. BBLN-1 interacts with IF proteins and localizes to the IF network in an IF-dependent manner. The appearance of invaginations is a result of the abnormal IF aggregation, indicating a direct role for the IF network in maintaining lumen homeostasis. Finally, we identify bublin (BBLN) as the mammalian ortholog of BBLN-1. When expressed in the C. elegans intestine, bublin recapitulates the localization pattern of BBLN-1 and can compensate for the loss of BBLN-1. In mouse intestinal organoids, bublin localizes subapically, together with the IF protein keratin 8. Our results therefore may have implications for understanding the role of IFs in regulating epithelial tube morphology in mammals.SummaryWe identify BBLN-1 as an evolutionary conserved regulator of lumen morphology in the C. elegans intestine. Loss of bbln-1 causes intermediate filament network reorganization that induces severe apical morphology defects. We also identify bublin (BBLN) as the mammalian ortholog, which can compensate for the loss of BBLN-1 in C. elegans.

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The novel intestinal filament organizer IFO-1 contributes to epithelial integrity in concert with ERM-1 and DLG-1

Cited by 5 publications

References 1 publication

Disruption of the C. elegans Intestinal Brush Border by the Fungal Lectin CCL2 Phenocopies Dietary Lectin Toxicity in Mammals

Disruption of the C. elegans Intestinal Brush Border by the Fungal Lectin CCL2 Phenocopies Dietary Lectin Toxicity in Mammals

Intracellular Motility of Intermediate Filaments

BBLN-1 is essential for intermediate filament organization and apical membrane morphology

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