RhoGAP19D inhibits Cdc42 laterally to control epithelial cell shape and prevent invasion
Cdc42-GTP is required for apical domain formation in epithelial cells, where it recruits and activates the Par-6-aPKC polarity complex, but how the activity of Cdc42 itself is restricted apically is unclear. We used sequence analysis and 3D structural modeling to determine which Drosophila GTPase-ac...
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| Main Authors: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
March 01 2021
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| In: |
The journal of cell biology
Year: 2021, Volume: 220, Issue: 4, Pages: 1-22 |
| ISSN: | 1540-8140 |
| DOI: | 10.1083/jcb.202009116 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1083/jcb.202009116
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| Author Notes: | Weronika Fic, Rebecca Bastock, Francesco Raimondi, Erinn Los, Yoshiko Inoue, Jennifer L. Gallop, Robert B. Russell, and Daniel St Johnston |
MARC
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| 245 | 1 | 0 | |a RhoGAP19D inhibits Cdc42 laterally to control epithelial cell shape and prevent invasion |c Weronika Fic, Rebecca Bastock, Francesco Raimondi, Erinn Los, Yoshiko Inoue, Jennifer L. Gallop, Robert B. Russell, and Daniel St Johnston |
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| 520 | |a Cdc42-GTP is required for apical domain formation in epithelial cells, where it recruits and activates the Par-6-aPKC polarity complex, but how the activity of Cdc42 itself is restricted apically is unclear. We used sequence analysis and 3D structural modeling to determine which Drosophila GTPase-activating proteins (GAPs) are likely to interact with Cdc42 and identified RhoGAP19D as the only high-probability Cdc42GAP required for polarity in the follicular epithelium. RhoGAP19D is recruited by α-catenin to lateral E-cadherin adhesion complexes, resulting in exclusion of active Cdc42 from the lateral domain. rhogap19d mutants therefore lead to lateral Cdc42 activity, which expands the apical domain through increased Par-6/aPKC activity and stimulates lateral contractility through the myosin light chain kinase, Genghis khan (MRCK). This causes buckling of the epithelium and invasion into the adjacent tissue, a phenotype resembling that of precancerous breast lesions. Thus, RhoGAP19D couples lateral cadherin adhesion to the apical localization of active Cdc42, thereby suppressing epithelial invasion. | ||
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| 700 | 1 | |a Los, Erinn |e VerfasserIn |4 aut | |
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| 700 | 1 | |a Gallop, Jennifer L. |e VerfasserIn |4 aut | |
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| 700 | 1 | |a St Johnston, Daniel |e VerfasserIn |4 aut | |
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