A Sensitized Screen for Genes Promoting Invadopodia Function In Vivo: CDC-42 and Rab GDI-1 Direct Distinct Aspects of Invadopodia Formation

• DOI: 10.1371/journal.pgen.1005786
• Publication Date: 2016-01-15T02:22:26Z
• Authors: Lauren L. Lohmer; Matthew R. Clay; Kaleb M. Naegeli; Qiuyi Chi; Joshua W. Ziel; Elliott J. Hagedorn; Jieun E. Park; Ranjay Jayadev; David R. Sherwood
• Keywords: Invadopodia; Rab; Podosome; Pseudopodia

Invadopodia are specialized membrane protrusions composed of F-actin, actin regulators, signaling proteins, and a dynamically trafficked invadopodial that drive cell invasion through basement (BM) barriers in development cancer. Due to the challenges studying vivo, mechanisms controlling invadopodia formation their native environments remain poorly understood. We performed sensitized genome-wide RNAi screen identified 13 potential regulators during anchor (AC) into vulval epithelium C. elegans. Confirming specificity this screen, we Rho GTPase cdc-42, which mediates many cancer lines. Using live-cell imaging, show CDC-42 localizes AC-BM interface is activated by an unidentified signal(s) induces invasion. required for invasive localization WSP-1 (N-WASP), effector promotes polymerization F-actin. Loss or resulted fewer delayed BM breaching. also characterized novel regulator, gdi-1 (Rab GDP dissociation inhibitor), trafficking. GDI-1 functions AC promote formation. In absence GDI-1, was no longer normally membrane, instead distributed plasma throughout cell. Surprisingly, pro-invasive from cells controls activity These studies represent first vivo genes regulating demonstrate requires integration distinct cellular processes coordinated extracellular cue.