Cell Invasion In Vivo via Rapid Exocytosis of a Transient Lysosome-Derived Membrane Domain.
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.
Duke Scholars
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Related Subject Headings
- Nerve Tissue Proteins
- Lysosomes
- Gene Expression Regulation, Developmental
- Exocytosis
- Developmental Biology
- Cell Movement
- Cell Membrane
- Caenorhabditis elegans Proteins
- Caenorhabditis elegans
- Basement Membrane
Citation
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Nerve Tissue Proteins
- Lysosomes
- Gene Expression Regulation, Developmental
- Exocytosis
- Developmental Biology
- Cell Movement
- Cell Membrane
- Caenorhabditis elegans Proteins
- Caenorhabditis elegans
- Basement Membrane