Format

Send to

Choose Destination
Nat Cell Biol. 2009 Feb;11(2):183-9. doi: 10.1038/ncb1825. Epub 2008 Dec 21.

UNC-6 (netrin) orients the invasive membrane of the anchor cell in C. elegans.

Author information

1
Department of Biology, Duke University, Box 90338, Durham, NC 27708, USA.

Abstract

Despite their profound importance in the development of cancer, the extracellular cues that target cell invasion through basement membrane barriers remain poorly understood. A central obstacle has been the difficulty of studying the interactions between invading cells and basement membranes in vivo. Using the genetically and visually tractable model of Caenorhabditis elegans anchor cell (AC) invasion, we show that UNC-6 (netrin) signalling, a pathway not previously implicated in controlling cell invasion in vivo, is a key regulator of this process. Site of action studies reveal that before invasion, localized UNC-6 secretion directs its receptor, UNC-40, to the plasma membrane of the AC, in contact with the basement membrane. There, UNC-40 polarizes a specialized invasive membrane domain through the enrichment of actin regulators, F-actin and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)). Cell ablation experiments indicate that UNC-6 promotes the formation of invasive protrusions from the AC that break down the basement membrane in response to a subsequent vulval cue. Together, these results characterize an invasive membrane domain in vivo, and reveal a role for UNC-6 (netrin) in polarizing this domain towards its basement membrane target.

PMID:
19098902
PMCID:
PMC2635427
DOI:
10.1038/ncb1825
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center