ADF/cofilin promotes invadopodial membrane recycling during cell invasion in vivo.
Journal Article (Journal Article)
Invadopodia are protrusive, F-actin-driven membrane structures that are thought to mediate basement membrane transmigration during development and tumor dissemination. An understanding of the mechanisms regulating invadopodia has been hindered by the difficulty of examining these dynamic structures in native environments. Using an RNAi screen and live-cell imaging of anchor cell (AC) invasion in Caenorhabditis elegans, we have identified UNC-60A (ADF/cofilin) as an essential regulator of invadopodia. UNC-60A localizes to AC invadopodia, and its loss resulted in a dramatic slowing of F-actin dynamics and an inability to breach basement membrane. Optical highlighting indicated that UNC-60A disassembles actin filaments at invadopodia. Surprisingly, loss of unc-60a led to the accumulation of invadopodial membrane and associated components within the endolysosomal compartment. Photobleaching experiments revealed that during normal invasion the invadopodial membrane undergoes rapid recycling through the endolysosome. Together, these results identify the invadopodial membrane as a specialized compartment whose recycling to form dynamic, functional invadopodia is dependent on localized F-actin disassembly by ADF/cofilin.
- Hagedorn, EJ; Kelley, LC; Naegeli, KM; Wang, Z; Chi, Q; Sherwood, DR
- March 2014
Volume / Issue
- 204 / 7
Start / End Page
- 1209 - 1218
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)
International Standard Serial Number (ISSN)
Digital Object Identifier (DOI)