Time to make the doughnuts: Building and shaping seamless tubes

Sundaram, Meera V.; Cohen, Jozef

doi:10.1016/j.semcdb.2016.05.006

Cited by 38 publications

(49 citation statements)

References 108 publications

(219 reference statements)

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“…1C) or they can be branched and terminated by dead ends, as observed for the excretory canal cell in C. elegans or the tracheal terminal cell in Drosophila [ 77 , 78 ]. Both endocytic and exocytic trafficking mechanisms have been implicated in generating the internal apical domain of seamless tubes [ 77 ]. Another mechanism for forming a seamless tube involves converting a seamed tube to a seamless tube via auto-fusion (Fig.…”

Section: Formation Of Seamless Tubes By Auto-fusionmentioning

confidence: 99%

Auto-fusion and the shaping of neurons and tubes

Soulavie

Sundaram

2016

Seminars in Cell & Developmental Biology

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Cells adopt specific shapes that are necessary for specific functions. For example, some neurons extend elaborate arborized dendrites that can contact multiple targets. Epithelial and endothelial cells can form tiny seamless unicellular tubes with an intracellular lumen. Recent advances showed that cells can auto-fuse to acquire those specific shapes. During auto-fusion, a cell merges two parts of its own plasma membrane. In contrast to cell-cell fusion or macropinocytic fission, which result in the merging or formation of two separate membrane bound compartments, auto-fusion preserves one compartment, but changes its shape. The discovery of auto-fusion in C. elegans was enabled by identification of specific protein fusogens, EFF-1 and AFF-1, that mediate cell-cell fusion. Phenotypic characterization of eff-1 and aff-1 mutants revealed that fusogen-mediated fusion of two parts of the same cell can be used to sculpt dendritic arbors, reconnect two parts of an axon after injury, or form a hollow unicellular tube. Similar auto-fusion events recently were detected in vertebrate cells, suggesting that auto-fusion could be a widely used mechanism for shaping neurons and tubes.

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Section: Formation Of Seamless Tubes By Auto-fusionmentioning

confidence: 99%

Auto-fusion and the shaping of neurons and tubes

Soulavie

Sundaram

2016

Seminars in Cell & Developmental Biology

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“…Cytoskeletal components play an essential role in maintaining canal structure (SUNDARAM and COHEN 2017). Actin filaments are aligned over the apical surface of the canal lumen and docked to apical membrane via the ezrin/radixin/moesin homologue ERM-1 (GÖBEL et al 2004) and the apical β H spectrin (PRAITIS et al 2005), while mutations in the formin gene exc-6 compromise nucleation of microtubules along the length of the canal (SHAYE and GREENWALD 2015).…”

Section: Introductionmentioning

confidence: 99%

Intermediate filaments EXC-2 and IFA-4 Maintain Luminal Structure of the Tubular Excretory Canals inCaenorhabditis elegans

Al-Hashimi

Hall

Ackley

et al. 2018

Preprint

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C. elegans excretory canals form a useful model for understanding formation of narrow 33 tubes. exc-2 mutants start to form normal canals that then swell into fluid-filled cysts. We show 34 that exc-2 encodes a large intermediate filament (IF) protein previously not thought to be located 35 in the canals. EXC-2 is located at the apical (luminal) membrane, binds to another IF protein, 36 and appears to be one of three IF proteins that form a flexible meshwork to maintain the thin 37 canal diameter. This work provides a genetically useful model for understanding the interactions 38 of IF proteins with other cytoskeletal elements to regulate tube size and growth. 39 3 ABSTRACT 40 The excretory canals of Caenorhabditis elegans are a model for understanding the maintenance 41 of apical morphology in narrow single-celled tubes. Light and electron microscopy shows that 42 mutants in exc-2 start to form canals normally, but these swell to develop large fluid-filled cysts 43 that lack a complete terminal web at the apical surface, and accumulate filamentous material in 44 the canal lumen. Here, whole-genome sequencing and gene rescue show that exc-2 encodes 45 intermediate filament protein IFC-2. EXC-2/IFC-2 protein, fluorescently tagged via 46 CRISPR/Cas9, is located at the apical surface of the canals independently of other intermediate 47 filament proteins. EXC-2 is also located in several other tissues, though the tagged isoforms are 48 not seen in the larger intestinal tube. Tagged EXC-2 binds via pulldown to intermediate filament 49 protein IFA-4, which is also shown to line the canal apical surface. Overexpression of either 50 protein results in narrow but shortened canals. These results are consistent with a model 51 whereby three intermediate filaments in the canals, EXC-2, IFA-4, and IFB-1, restrain swelling 52 of narrow tubules in concert with actin filaments that guide the extension and direction of tubule 53 outgrowth, while allowing the tube to bend as the animal moves. 54 93 While most of the original exc genes have been cloned (GRUSSENDORF et al. 2016; 94 SUNDARAM and BUECHNER 2016), mutations in the exc-2 gene cause particularly severe canal 95 defects. In these mutants, the canal length is shortened by over half, the animals accumulate 96 multiple cysts in the canals, and are sensitive to growth at low osmolarity (BUECHNER et al. 97 1999). Four alleles of this gene were discovered in the original screen, which suggested that it 98 encodes a large protein. Here we report that exc-2 encodes the intermediate filament IFC-2, and 99 additionally found that mutations in the ifa-4 intermediate filament gene also cause cystic canal 100 6 defects similar to those of exc-2 mutants. Overexpression of either exc-2 or ifa-4 results in 101 shortened canals with small or no cysts. EXC-2 and IFA-4 proteins bind to each other and are 102 located at the apical membrane of the canals. The position of EXC-2 at the apical membrane 103 occurs independently of IFB-1 and IFA-4 function in the canals. These result...

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“…The EC is a 'seamless' tube that does not have adherens or tight junctions along its length; instead, it has a junction where it connects to its neighboring cell. Such seamless tubes are found in vertebrate vascular systems, as well as in invertebrate organs and glia (Sundaram and Cohen, 2016).…”

Section: Introductionmentioning

confidence: 99%

A network of conserved formins, regulated by the guanine exchange factor EXC-5 and the GTPase CDC-42, modulates tubulogenesis in vivo

Shaye

Greenwald

2016

Development

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The C. elegans excretory cell (EC) is a powerful model for tubulogenesis, a conserved process that requires precise cytoskeletal regulation. EXC-6, an ortholog of the diseaseassociated formin INF2, coordinates cell outgrowth and lumen formation during EC tubulogenesis by regulating F-actin at the tip of the growing canal and the dynamics of basolateral microtubules. EXC-6 functions in parallel with EXC-5/FGD, a predicted activator of the Rho GTPase Cdc42. Here, we identify the parallel pathway: EXC-5 functions through CDC-42 to regulate two other formins: INFT-2, another INF2 ortholog, and CYK-1, the sole ortholog of the mammalian diaphanous (mDia) family of formins. We show that INFT-2 promotes F-actin accumulation in the EC, and that CYK-1 inhibits INFT-2 to regulate F-actin levels and EXC-6-promoted outgrowth. As INF2 and mDia physically interact and cross-regulate in cultured cells, our work indicates that a conserved EXC-5−CDC-42 pathway modulates this regulatory interaction and that it is functionally important in vivo during tubulogenesis.

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Time to make the doughnuts: Building and shaping seamless tubes

Cited by 38 publications

References 108 publications

Auto-fusion and the shaping of neurons and tubes

Auto-fusion and the shaping of neurons and tubes

Intermediate filaments EXC-2 and IFA-4 Maintain Luminal Structure of the Tubular Excretory Canals inCaenorhabditis elegans

A network of conserved formins, regulated by the guanine exchange factor EXC-5 and the GTPase CDC-42, modulates tubulogenesis in vivo

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