Buchumschlag

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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Bibliographische Detailangaben
Hauptverfasser: Fic, Weronika (VerfasserIn) , Bastock, Rebecca (VerfasserIn) , Raimondi, Francesco (VerfasserIn) , Los, Erinn (VerfasserIn) , Inoue, Yoshiko (VerfasserIn) , Gallop, Jennifer L. (VerfasserIn) , Russell, Robert B. (VerfasserIn) , St Johnston, Daniel (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: March 01 2021
In: The journal of cell biology
Year: 2021, Jahrgang: 220, Heft: 4, Pages: 1-22
ISSN:1540-8140
DOI:10.1083/jcb.202009116
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1083/jcb.202009116
Volltext
Verfasserangaben:Weronika Fic, Rebecca Bastock, Francesco Raimondi, Erinn Los, Yoshiko Inoue, Jennifer L. Gallop, Robert B. Russell, and Daniel St Johnston
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 20.07.2021
Beschreibung:Online Resource
ISSN:1540-8140
DOI:10.1083/jcb.202009116

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