De novo lipid synthesis and polarized prenylation promote invasive protrusion formation. (A) A schematic diagram summarizing AC invasion. Invadosomes form and one breaches the underlying BM. The netrin receptor DCC (UNC-40) enriches at the BM breach site and directs lysosomal exocytosis, which provides membrane for protrusion growth. AC invasive protrusion growth is facilitated by the enrichment of GPI-anchored matrix degrading metalloproteinase ZMP-1 and prenylated Rac and Ras-like GTPases that direct F-actin formation. (B) A schematic diagram highlighting the roles and regulation of de novo lipid synthesis and lipid prenylation during AC invasive protrusion formation. Nuclear SBP-1 promotes expression of the fatty acid synthesis enzymes pod-2 and fasn-1 that provide fatty acid substrates for LPIN-1 and SMS-1, which synthesize phospholipids and sphingomyelin that build lysosome stores for the protrusion. Sphingomyelin, which is a key component of lipid rafts, is also required for the enrichment of the UNC-40 receptor and the GPI-anchored metalloprotease ZMP-1, which both partition to lipid rafts. Sphingomyelin and phospholipids are delivered to the protrusion via lysosomes. A specialized prenylation system, where the intermediate enzyme FCE-1 localizes to ER and peroxisomes and the final enzyme of prenylation, ICMT-1, localizes to ER exit sites (ERES), rapidly delivers Rac- and Ras-like GTPases to the AC invasive front to direct protrusion growth. Phospholipids and prenylated proteins might also be delivered directly to the invasive protrusion from the ER (magenta arrows).