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Tre1 GPCR initiates germ cell transepithelial migration by regulating Drosophila melanogaster E-cadherin

Kunwar, Prabhat S. and Sano, Hiroko and Renault, Andrew D. and Barbosa, Vitor and Fuse, Naoyuki and Lehmann, Ruth (2008) Tre1 GPCR initiates germ cell transepithelial migration by regulating Drosophila melanogaster E-cadherin. Journal of Cell Biology, 183 (1). pp. 157-168. ISSN 0021-9525. PMCID PMC2557050. https://resolver.caltech.edu/CaltechAUTHORS:KUNjcb08

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Image (JPEG) (Figure S1. Dispersal and amoeboid migration of wild-type and tre1 mutant germ cells.) - Supplemental Material
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Image (JPEG) (Figure S2. Dispersal and amoeboid migration of wild-type germ cells.) - Supplemental Material
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Image (JPEG) (Figure S3. Accumulation of β-catenin and α-catenin in the tail of wild-type germ cells.) - Supplemental Material
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Image (JPEG) (Figure S4. Phenotype of shgA9-49 in late embryogenesis.) - Supplemental Material
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[img] Video (QuickTime) (Video 1. Wild-type germ cells during the blastoderm stage (lateral view).) - Supplemental Material
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[img] Video (QuickTime) (Video 2 Wild-type germ cells during the gastrulation stage (lateral view).) - Supplemental Material
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[img] Video (QuickTime) (Video 3 Transepithelial migration of germ cells in the wild-type embryo (dorsal view).) - Supplemental Material
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[img] Video (QuickTime) (Video 4 Transepithelial migration of germ cells in the wild-type embryo (dorsal view).) - Supplemental Material
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[img] Video (QuickTime) (Video 5 Transepithelial migration of germ cells in the tre1 mutant embryo (dorsal view).) - Supplemental Material
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PDF (Table S1 summarizes the expression patterns of the D. melanogaster G{alpha}, Gβ, and G{gamma} proteins and describes the respective loss-of-function phenotypes in general and in germ cells.) - Supplemental Material
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Abstract

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 Gβ 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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1083/jcb.200807049DOIArticle
http://jcb.rupress.org/cgi/content/abstract/183/1/157PublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2557050/PubMed CentralArticle
Additional Information:© 2008 Kunwar et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). Submitted: 9 July 2008. Accepted: 4 September 2008. Published September 29, 2008. We are particularly grateful to Dr. Daria Siekhaus for helpful discussion throughout this work and editing of the manuscript. We would like to thank the Bloomington Stock Center for fly stocks, and the Berkeley Drosophila Genome Project for sequence and in situ expression data. We also thank Drs. Mike Dustin and Wenbio Gan, and their laboratory members for help with two-photon microscopy; and Dr. Frank Macaluso, Leslie Gunther, and Juan Jimenez of the Albert Einstein College of Medicine Analytical Imaging Center for assistance with electron microscopy. We are grateful to all members of the Lehmann laboratory, particularly the member of the 2R screen (Alexey Arkov, Elena Arkova, Helene Zinszner, and Thomas Marty) for isolating the shgA9-49 allele. We are also grateful to Drs. Holger Knaut and Thomas Marty for discussions. This work was supported by National Institutes of Health grant HD49100. A.D. Renault was a Charles H. Revson Senior Fellow in Biomedical Science, V. Barbosa was supported by the Fundação para a Ciência e Tecnologia, Portugal, and R. Lehmann is a Howard Hughes Medical Institute investigator and a member of the Kimmel Center for Stem Cell Biology. Online supplemental material: Fig. S1 shows electron micrographs demonstrating germ cell dispersal, interaction between germ cells and posterior midgut in the wild-type embryo, and tight association between germ cells, as well as the failure of germ cells to interact with midgut in tre1 mutant. Fig. S2 shows still images of a video showing dispersal and amoeboid migration of wild-type germ cells at the onset of transepithelial migration. Fig. S3 show that, like E-cadherin, β-catenin and {alpha}-catenin also accumulate in the tail of wild-type germ cells at stage 9. Fig. S4 shows additional phenotypes of shgA9-49 during later stages of embryogenesis, when germ cells separate into two bilateral clusters and associate with the somatic gonad. Table S1 summarizes the expression patterns of the D. melanogaster G{alpha}, Gβ, and G{gamma} proteins and describes the respective loss-of-function phenotypes in general and in germ cells. Video 1 shows behavior of wild-type germ cells during the blastoderm stage. Video 2 shows behavior of wild-type germ cells during the gastrulation stage. Video 3 shows polarization and transepithelial migration of germ cells in a wild-type embryo. Video 4 shows the transepithelial migration of germ cells with long extensions in a wild-type embryo. Video 5 shows transepithelial migration of germ cells in an embryo from a tre1 mutant female. Online supplemental material is available at http://www.jcb.org/cgi/content/full/jcb.200807049/DC1.
Funders:
Funding AgencyGrant Number
National Institutes of HealthHD49100
Charles H. Revson FoundationUNSPECIFIED
Fundação para a Ciência e Tecnologia (Portugal)UNSPECIFIED
Howard Hughes Medical InstituteUNSPECIFIED
Kimmel Center for Stem Cell BiologyUNSPECIFIED
Issue or Number:1
PubMed Central ID:PMC2557050
Record Number:CaltechAUTHORS:KUNjcb08
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:KUNjcb08
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:11806
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:30 Sep 2008 05:32
Last Modified:03 Oct 2019 00:22

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