Integrin acts upstream of netrin signaling to regulate formation of the anchor cell's invasive membrane in C. elegans.
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.
Hagedorn
Elliott J
EJ
Department of Biology, Duke University, Science Drive, Box 90388, Durham, NC 27708, USA.
Yashiro
Hanako
H
Ziel
Joshua W
JW
Ihara
Shinji
S
Wang
Zheng
Z
Sherwood
David R
DR
D000818:Animals; D030801:Animals, Genetically Modified; D001485:Basement Membrane / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity; D005838:Genotype; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D000075388:Netrin-1; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D015815:Cell Adhesion Molecules; C520083:FOS-1 protein, C elegans; C521951:Ina-1 protein, C elegans; D016023:Integrins; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D016760:Proto-Oncogene Proteins c-fos; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; C102174:UNC-40 protein, C elegans; C424064:him-4 protein, C elegans; D000075388:Netrin-1
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