ArticleMolecular and cellular biology2017
A Two-Tiered Mechanism Enables Localized Cdc42 Signaling during Enterocyte Polarization.
Article in Molecular and cellular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 13 citations in OpenAlex.
- Molecular subversion of Cdc42 signalling in cancer.Biochemical Society transactions · 2021Review
- Tuba Activates Cdc42 during Neuronal Polarization Downstream of the Small GTPase Rab8a.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Article
- Profilin-Mediated Actin Allocation Regulates the Growth of Epithelial Microvilli.Current biology : CB · 2019Article
- Autoactivation of small GTPases by the GEF-effector positive feedback modules.F1000Research · 2019Review
- A Tuba/Cdc42/Par6A complex is required to ensure singularity in apical domain formation during enterocyte polarization.PloS one · 2018Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signaling by the small GTPase Cdc42 governs a diverse set of cellular processes that contribute to tissue morphogenesis. Since these processes often require highly localized signaling, Cdc42 activity must be clustered in order to prevent ectopic signaling. During cell polarization, apical Cdc42 signaling directs the positioning of the nascent apical membrane. However, the molecular mechanisms that drive Cdc42 clustering during polarity establishment are largely unknown. Here, we demonstrate that during cell polarization localized Cdc42 signaling is enabled via activity-dependent control of Cdc42 mobility. By performing photoconversion experiments, we show that inactive Cdc42-GDP is 30-fold more mobile than active Cdc42-GTP. This switch in apical mobility originates from a dual mechanism involving RhoGDI-mediated membrane dissociation of Cdc42-GDP and Tuba-mediated immobilization of Cdc42-GTP. Interference with either mechanism affects Cdc42 clustering and as a consequence impairs Cdc42-mediated apical membrane clustering. We therefore identify a molecular network, comprised of Cdc42, the guanine nucleotide exchange factor (GEF) Tuba, and RhoGDI, that enables differential diffusion of inactive and active Cdc42 and is required to establish localized Cdc42 signaling during enterocyte polarization.
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