The Dlg Module and Clathrin-Mediated Endocytosis Regulate EGFR Signaling and Cyst Cell-Germline Coordination in the Drosophila Testis
Summary: Tissue homeostasis and repair relies on proper communication of stem cells and their differentiating daughters with the local tissue microenvironment. In the Drosophila male germline adult stem cell lineage, germ cells proliferate and progressively differentiate enclosed in supportive somat...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-05-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671119300931 |
| _version_ | 1818152077879148544 |
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| author | Fani Papagiannouli Cameron Wynn Berry Margaret T. Fuller |
| author_facet | Fani Papagiannouli Cameron Wynn Berry Margaret T. Fuller |
| author_sort | Fani Papagiannouli |
| collection | DOAJ |
| description | Summary: Tissue homeostasis and repair relies on proper communication of stem cells and their differentiating daughters with the local tissue microenvironment. In the Drosophila male germline adult stem cell lineage, germ cells proliferate and progressively differentiate enclosed in supportive somatic cyst cells, forming a small organoid, the functional unit of differentiation. Here we show that cell polarity and vesicle trafficking influence signal transduction in cyst cells, with profound effects on the germ cells they enclose. Our data suggest that the cortical components Dlg, Scrib, Lgl and the clathrin-mediated endocytic (CME) machinery downregulate epidermal growth factor receptor (EGFR) signaling. Knockdown of dlg, scrib, lgl, or CME components in cyst cells resulted in germ cell death, similar to increased signal transduction via the EGFR, while lowering EGFR or downstream signaling components rescued the defects. This work provides insights into how cell polarity and endocytosis cooperate to regulate signal transduction and sculpt developing tissues. : In this article, Papagiannouli and colleagues show that Dlg, Scrib, Lgl, and clathrin-mediated endocytosis downregulate EGFR signaling levels in the somatic cyst cells of the Drosophila testis. Knockdown of their function in cyst cells results in cell non-autonomous apoptosis of the neighboring germline and increased levels of the EGFR downstream effector MAPK, mediated in part by the membrane phospholipid PIP2. Keywords: Drosophila spermatogenesis, dlg, scrib, lgl, endocytosis, polarity, EGFR regulation, clathrin, PIP2, septate junctions |
| first_indexed | 2024-12-11T13:48:59Z |
| format | Article |
| id | doaj.art-2d19b8c605e34113ab4aef9ee59f6468 |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-11T13:48:59Z |
| publishDate | 2019-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-2d19b8c605e34113ab4aef9ee59f64682022-12-22T01:04:21ZengElsevierStem Cell Reports2213-67112019-05-0112510241040The Dlg Module and Clathrin-Mediated Endocytosis Regulate EGFR Signaling and Cyst Cell-Germline Coordination in the Drosophila TestisFani Papagiannouli0Cameron Wynn Berry1Margaret T. Fuller2Department of Developmental Biology, Beckman Center, Stanford University School of Medicine, Stanford, CA 94305-5329, USA; Institute for Genetics, University of Cologne, 50674 Cologne, Germany; Corresponding authorDepartment of Developmental Biology, Beckman Center, Stanford University School of Medicine, Stanford, CA 94305-5329, USADepartment of Developmental Biology, Beckman Center, Stanford University School of Medicine, Stanford, CA 94305-5329, USASummary: Tissue homeostasis and repair relies on proper communication of stem cells and their differentiating daughters with the local tissue microenvironment. In the Drosophila male germline adult stem cell lineage, germ cells proliferate and progressively differentiate enclosed in supportive somatic cyst cells, forming a small organoid, the functional unit of differentiation. Here we show that cell polarity and vesicle trafficking influence signal transduction in cyst cells, with profound effects on the germ cells they enclose. Our data suggest that the cortical components Dlg, Scrib, Lgl and the clathrin-mediated endocytic (CME) machinery downregulate epidermal growth factor receptor (EGFR) signaling. Knockdown of dlg, scrib, lgl, or CME components in cyst cells resulted in germ cell death, similar to increased signal transduction via the EGFR, while lowering EGFR or downstream signaling components rescued the defects. This work provides insights into how cell polarity and endocytosis cooperate to regulate signal transduction and sculpt developing tissues. : In this article, Papagiannouli and colleagues show that Dlg, Scrib, Lgl, and clathrin-mediated endocytosis downregulate EGFR signaling levels in the somatic cyst cells of the Drosophila testis. Knockdown of their function in cyst cells results in cell non-autonomous apoptosis of the neighboring germline and increased levels of the EGFR downstream effector MAPK, mediated in part by the membrane phospholipid PIP2. Keywords: Drosophila spermatogenesis, dlg, scrib, lgl, endocytosis, polarity, EGFR regulation, clathrin, PIP2, septate junctionshttp://www.sciencedirect.com/science/article/pii/S2213671119300931 |
| spellingShingle | Fani Papagiannouli Cameron Wynn Berry Margaret T. Fuller The Dlg Module and Clathrin-Mediated Endocytosis Regulate EGFR Signaling and Cyst Cell-Germline Coordination in the Drosophila Testis Stem Cell Reports |
| title | The Dlg Module and Clathrin-Mediated Endocytosis Regulate EGFR Signaling and Cyst Cell-Germline Coordination in the Drosophila Testis |
| title_full | The Dlg Module and Clathrin-Mediated Endocytosis Regulate EGFR Signaling and Cyst Cell-Germline Coordination in the Drosophila Testis |
| title_fullStr | The Dlg Module and Clathrin-Mediated Endocytosis Regulate EGFR Signaling and Cyst Cell-Germline Coordination in the Drosophila Testis |
| title_full_unstemmed | The Dlg Module and Clathrin-Mediated Endocytosis Regulate EGFR Signaling and Cyst Cell-Germline Coordination in the Drosophila Testis |
| title_short | The Dlg Module and Clathrin-Mediated Endocytosis Regulate EGFR Signaling and Cyst Cell-Germline Coordination in the Drosophila Testis |
| title_sort | dlg module and clathrin mediated endocytosis regulate egfr signaling and cyst cell germline coordination in the drosophila testis |
| url | http://www.sciencedirect.com/science/article/pii/S2213671119300931 |
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