Netrin Stabilizes UNC-40(DCC)-Generated Oscillatory Polarity to Direct Anchor Cell Invasion in C. elegans
Asymmetrical localization of cellular constituents in the specific membrane domains is a critical step for many biological processes, including cell invasion through basement membrane (BM). Netrin signaling mediates the formation of a variety of specialized membrane domains in multicellular organisms. However, how netrin signaling polarizes these domains remain largely unknown. Using the genetically and visually accessible model of anchor cell (AC) invasion in C. elegans, we have recently shown that UNC-6 polarizes a specialized invasive cell membrane domain toward the BM. Here, we demonstrate that UNC-6 polarizes this domain by stabilizing and orienting an UNC-40-mediated polarity oscillation. Our data show that UNC-40 is active in the absence of UNC-6. The live-cell imaging analysis reveals that active UNC-40 forms dynamic clusters inducing a random periodic F-actin disassembly and assembly through its downstream effectors, thereby generating an oscillatory polarity. These results suggest a general mechanism that allows UNC-40 (DCC) to direct exploratory behavior to rapidly detect and direct polarized responses toward sources of UNC-6 (Netrin).
Wang, Z; Ziel, JW; Chi, Q; Hagedorn, EJ; Sherwood, DR