A tensile trilayered cytoskeletal endotube drives capillary-like lumenogenesis

J Cell Biol. 2019 Jul 1;218(7):2403-2424. doi: 10.1083/jcb.201811175. Epub 2019 Jun 25.

Abstract

Unicellular tubes are components of internal organs and capillaries. It is unclear how they meet the architectural challenge to extend a centered intracellular lumen of uniform diameter. In an RNAi-based Caenorhabditis elegans screen, we identified three intermediate filaments (IFs)-IFA-4, IFB-1, and IFC-2-as interactors of the lumenal membrane-actin linker ERM-1 in excretory-canal tubulogenesis. We find that IFs, generally thought to affect morphogenesis indirectly by maintaining tissue integrity, directly promote lumenogenesis in this capillary-like single-cell tube. We show that ERM-1, ACT-5/actin, and TBB-2/tubulin recruit membrane-forming endosomal and flux-promoting canalicular vesicles to the lumen, whereas IFs, themselves recruited to the lumen by ERM-1 and TBB-2, restrain lateral vesicle access. IFs thereby prevent cystogenesis, equilibrate the lumen diameter, and promote lumen forward extension. Genetic and imaging analyses suggest that IFB-1/IFA-4 and IFB-1/IFC-2 polymers form a perilumenal triple IF lattice, sandwiched between actin and helical tubulin. Our findings characterize a novel mechanism of capillary-like lumenogenesis, where a tensile trilayered cytoskeletal endotube transforms concentric into directional growth.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans Proteins / genetics*
  • Capillaries / growth & development
  • Capillaries / metabolism
  • Cytoskeletal Proteins
  • Cytoskeleton / genetics
  • Intermediate Filament Proteins / genetics*
  • Intermediate Filaments / genetics*
  • Morphogenesis / genetics
  • RNA Interference
  • Tubulin / genetics

Substances

  • ACT-5 protein, C elegans
  • Actins
  • Caenorhabditis elegans Proteins
  • Cytoskeletal Proteins
  • ERM-1 protein, C elegans
  • IFA-4 protein, C elegans
  • IFB-1 protein, C elegans
  • IFC-2 protein, C elegans
  • Intermediate Filament Proteins
  • Tubulin