Integrin Acts Upstream of Netrin Signaling to Regulate Formation of the Anchor Cell's Invasive Membrane in C. elegans

Department of Biology, Duke University, Science Drive, Box 90388, Durham, NC 27708, USA.
Developmental Cell (Impact Factor: 9.71). 09/2009; 17(2):187-98. DOI: 10.1016/j.devcel.2009.06.006
Source: PubMed


Integrin expression and activity have been strongly correlated with developmental and pathological processes involving cell invasion through basement membranes. The role of integrins in mediating these invasions, however, remains unclear. Utilizing the genetically and visually accessible model of anchor cell (AC) invasion in C. elegans, we have recently shown that netrin signaling orients a specialized invasive cell membrane domain toward the basement membrane. Here, we demonstrate that the integrin heterodimer INA-1/PAT-3 plays a crucial role in AC invasion, in part by targeting the netrin receptor UNC-40 (DCC) to the AC's plasma membrane. Analyses of the invasive membrane components phosphatidylinositol 4,5-bisphosphate, the Rac GTPase MIG-2, and F-actin further indicate that INA-1/PAT-3 plays a broad role in promoting the plasma membrane association of these molecules. Taken together, these studies reveal a role for integrin in regulating the plasma membrane targeting and netrin-dependent orientation of a specialized invasive membrane domain.

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    • "Thus, rather than complex endpoint phenotypes, live cell approaches allow examination of normal and disrupted cellular behaviors as they occur. For example, using live imaging we have shown that the integrin cell–matrix receptor has independent functions in both mediating cell–basement membrane attachment and establishing a specialized cell membrane domain that directs invasion through the basement membrane (Hagedorn et al., 2009; Wang et al., 2014). "
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    • "This same threshold was used in unc-40, unc-6, and madd-2; unc-6 mutants. Quantitative measurements were then made for the volume of fluorescent intensity with these isosurface renderings (Hagedorn et al., 2009). Isosurface renderings for mCherry::MoeABD in madd-2 mutants and wild-type animals shown in Fig. 8 were created with more stringent thresholds set to delineate ectopic and basal F-actin patches in madd-2 animals. "
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    • "Isosurface renderings of mCherry::moeABD were created using Imaris ''isosurface rendering'' function by setting a threshold that outlined the dense F-actin network. Quantitative measurements were made for the volume of fluorescent intensity within these isosurface renderings [19] "
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