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Citation
Fic, W., Bastock, R., Raimondi, F., Los, E., Inoue, Y., Gallop, J.L., Russell, R.B., St Johnston, D. (2021). RhoGAP19D inhibits Cdc42 laterally to control epithelial cell shape and prevent invasion.  J. Cell Biol. 220(4): e202009116.
FlyBase ID
FBrf0248225
Publication Type
Research paper
Abstract

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.

PubMed ID
PubMed Central ID
PMC7927664 (PMC) (EuropePMC)
Related Publication(s)
Personal communication to FlyBase

Location data for RhoGap19D deletions.
St Johnston, 2021.7.22, Location data for RhoGap19D deletions. [FBrf0249584]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    J. Cell Biol.
    Title
    Journal of Cell Biology
    Publication Year
    1966-
    ISBN/ISSN
    0021-9525
    Data From Reference