Cell Invasion In Vivo via Rapid Exocytosis of a Transient Lysosome-Derived Membrane Domain.
Journal Article (Journal Article)
Invasive cells use small invadopodia to breach basement membrane (BM), a dense matrix that encases tissues. Following the breach, a large protrusion forms to clear a path for tissue entry by poorly understood mechanisms. Using RNAi screening for defects in Caenorhabditis elegans anchor cell (AC) invasion, we found that UNC-6(netrin)/UNC-40(DCC) signaling at the BM breach site directs exocytosis of lysosomes using the exocyst and SNARE SNAP-29 to form a large protrusion that invades vulval tissue. Live-cell imaging revealed that the protrusion is enriched in the matrix metalloprotease ZMP-1 and transiently expands AC volume by more than 20%, displacing surrounding BM and vulval epithelium. Photobleaching and genetic perturbations showed that the BM receptor dystroglycan forms a membrane diffusion barrier at the neck of the protrusion, which enables protrusion growth. Together these studies define a netrin-dependent pathway that builds an invasive protrusion, an isolated lysosome-derived membrane structure specialized to breach tissue barriers.
Full Text
Duke Authors
Cited Authors
- Naegeli, KM; Hastie, E; Garde, A; Wang, Z; Keeley, DP; Gordon, KL; Pani, AM; Kelley, LC; Morrissey, MA; Chi, Q; Goldstein, B; Sherwood, DR
Published Date
- November 2017
Published In
Volume / Issue
- 43 / 4
Start / End Page
- 403 - 417.e10
PubMed ID
- 29161591
Pubmed Central ID
- PMC5726793
Electronic International Standard Serial Number (EISSN)
- 1878-1551
International Standard Serial Number (ISSN)
- 1534-5807
Digital Object Identifier (DOI)
- 10.1016/j.devcel.2017.10.024
Language
- eng