Tre1 GPCR initiates germ cell transepithelial migration by regulating Drosophila melanogaster E-cadherin.
Despite significant progress in identifying the guidance pathways that control cell migration, how a cell starts to move within an intact organism, acquires motility, and loses contact with its neighbors is poorly understood. We show that activation of the G protein-coupled receptor (GPCR) trapped in endoderm 1 (Tre1) directs the redistribution of the G protein Gbeta as well as adherens junction proteins and Rho guanosine triphosphatase from the cell periphery to the lagging tail of germ cells at the onset of Drosophila melanogaster germ cell migration. Subsequently, Tre1 activity triggers germ cell dispersal and orients them toward the midgut for directed transepithelial migration. A transition toward invasive migration is also a prerequisite for metastasis formation, which often correlates with down-regulation of adhesion proteins. We show that uniform down-regulation of E-cadherin causes germ cell dispersal but is not sufficient for transepithelial migration in the absence of Tre1. Our findings therefore suggest a new mechanism for GPCR function that links cell polarity, modulation of cell adhesion, and invasion.
Kunwar
Prabhat S
PS
Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016, USA.
Sano
Hiroko
H
Renault
Andrew D
AD
Barbosa
Vitor
V
Fuse
Naoyuki
N
Lehmann
Ruth
R
D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D004848:Epithelium / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D008854:Microscopy, Electron; D009154:Mutation; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D015820:Cadherins; D029721:Drosophila Proteins; D026901:Membrane Transport Proteins; D021122:Protein Subunits; D043562:Receptors, G-Protein-Coupled; D016212:Transforming Growth Factor beta; C410682:Tre1 protein, Drosophila; C089440:gbb protein, Drosophila; C071597:tud protein, Drosophila; D020962:Heterotrimeric GTP-Binding Proteins