Une nouvelle protéine RhoGAP impliquée dans la régulation du complexe Arp2/3 au niveau de l’appareil de Golgi : Un relais entre les protéines G ARF1 et Cdc42

Dubois, Thierry; Chavrier, Philippe

doi:10.1051/medsci/2005218-9692

Cited by 14 publications

(4 citation statements)

References 17 publications

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“…Here, Cdc42 cycles on or off the plasma membrane according to its active (GTP-bound) or inactive (GDP-bound) state respectively, where it promotes actin polymerization [8]. Cdc42 cycling is modulated by ARHGAP10, a Rho GTPase- activating-protein (GAP) that also harbours an Arf-binding domain which is specific for Arf-GTP (ABD; [10], [11]). Thus Cdc42–GAP activity, and actin-driven GEEC endocytosis is coupled to Arf1 activation [10].…”

Section: Introductionmentioning

confidence: 99%

Analysis of Endocytic Pathways in Drosophila Cells Reveals a Conserved Role for GBF1 in Internalization via GEECs

et al. 2009

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In mammalian cells, endocytosis of the fluid phase and glycosylphosphatidylinositol-anchored proteins (GPI-APs) forms GEECs (GPI-AP enriched early endosomal compartments) via an Arf1- and Cdc42-mediated, dynamin independent mechanism. Here we use four different fluorescently labeled probes and several markers in combination with quantitative kinetic assays, RNA interference and high resolution imaging to delineate major endocytic routes in Drosophila cultured cells. We find that the hallmarks of the pinocytic GEEC pathway are conserved in Drosophila and identify garz, the fly ortholog of the GTP exchange factor GBF1, as a novel component of this pathway. Live confocal and TIRF imaging reveals that a fraction of GBF1 GFP dynamically associates with ABD RFP (a sensor for activated Arf1 present on nascent pinosomes). Correspondingly, a GTP exchange mutant of GBF1 has altered ABD RFP localization in the evanescent field and is impaired in fluid phase uptake. Furthermore, GBF1 activation is required for the GEEC pathway even in the presence of Brefeldin A, implying that, like Arf1, it has a role in endocytosis that is separable from its role in secretion.

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Section: Introductionmentioning

confidence: 99%

Analysis of Endocytic Pathways in Drosophila Cells Reveals a Conserved Role for GBF1 in Internalization via GEECs

et al. 2009

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“…We also evidenced other transcripts such as cdc42ep (+1.62) coding for the CDC42EP2 which acts downstream of the Rho GTPase CDC42 to induce pseudopodia formation and play a decisive role in DL migration in vivo through adequate coordination of both cortical and non-cortical cytoskeletal flow [43]. Additionally we noted an increase of transcripts encoding for the GTPase activating protein ArhGAP10 (+2.15) which functions as GTPase-activating protein for Cdc42 and F-actin dynamics at the level of Golgi apparatus [44]. All together these results seem to indicate a modulation of components that sequentially elicit key changes in dynamics and in the architecture of cells, allowing coupled migration and maturation of DBA/2 live amastigotes-hosting DLs.…”

Section: Resultsmentioning

confidence: 80%

Distinct Transcriptional Signatures of Bone Marrow-Derived C57BL/6 and DBA/2 Dendritic Leucocytes Hosting Live Leishmania amazonensis Amastigotes

et al. 2012

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Background/ObjectivesThe inoculation of a low number (104) of L. amazonensis metacyclic promastigotes into the dermis of C57BL/6 and DBA/2 mouse ear pinna results in distinct outcome as assessed by the parasite load values and ear pinna macroscopic features monitored from days 4 to 22-phase 1 and from days 22 to 80/100-phase 2. While in C57BL/6 mice, the amastigote population size was increasing progressively, in DBA/2 mice, it was rapidly controlled. This latter rapid control did not prevent intracellular amastigotes to persist in the ear pinna and in the ear-draining lymph node/ear-DLN. The objectives of the present analysis was to compare the dendritic leukocytes-dependant immune processes that could account for the distinct outcome during the phase 1, namely, when phagocytic dendritic leucocytes of C57BL/6 and DBA/2 mice have been subverted as live amastigotes-hosting cells.Methodology/Principal FindingsBeing aware of the very low frequency of the tissues' dendritic leucocytes/DLs, bone marrow-derived C57BL/6 and DBA/2 DLs were first generated and exposed or not to live DsRed2 expressing L. amazonensis amastigotes. Once sorted from the four bone marrow cultures, the DLs were compared by Affymetrix-based transcriptomic analyses and flow cytometry. C57BL/6 and DBA/2 DLs cells hosting live L. amazonensis amastigotes do display distinct transcriptional signatures and markers that could contribute to the distinct features observed in C57BL/6 versus DBA/2 ear pinna and in the ear pinna-DLNs during the first phase post L. amazonensis inoculation.Conclusions/SignificanceThe distinct features captured in vitro from homogenous populations of C57BL/6 and DBA/2 DLs hosting live amastigotes do offer solid resources for further comparing, in vivo, in biologically sound conditions, functions that range from leukocyte mobilization within the ear pinna, the distinct emigration from the ear pinna to the DLN of live amastigotes-hosting DLs, and their unique signalling functions to either naive or primed T lymphocytes.

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“…Expression of the catalytically inactive PTEN CS-T383A construct that binds β-Arrestin1 but not the PTEN CS-A4 binding-defective mutant, enhanced Cdc42 - GTP levels in PTEN -/- cells ( Figure 6A,B ). While Cdc42 can be inhibited by ARHGAP21 ( Dubois and Chavrier, 2005 ), competitive β-Arrestin1 binding to the GAP domain can release the active GTPase from ARHGAP21 inhibition ( Anthony et al, 2011 ). To investigate the specific role of β-Arrestin1-ARHGAP21 interactions on Cdc42-dependent 3D morphogenesis, we used a cell-permeant 24-mer peptide analogue of the ARHGAP21 GAP domain that was designed to disrupt the β-Arrestin1-ARHGAP21 interaction ( Figure 6C ) ( Anthony et al, 2011 ).…”

Section: Resultsmentioning

confidence: 99%

PTEN controls glandular morphogenesis through a juxtamembrane β-Arrestin1/ARHGAP21 scaffolding complex

Javadi

Deevi

Evergren

et al. 2017

eLife

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PTEN controls three-dimensional (3D) glandular morphogenesis by coupling juxtamembrane signaling to mitotic spindle machinery. While molecular mechanisms remain unclear, PTEN interacts through its C2 membrane-binding domain with the scaffold protein β-Arrestin1. Because β-Arrestin1 binds and suppresses the Cdc42 GTPase-activating protein ARHGAP21, we hypothesize that PTEN controls Cdc42 -dependent morphogenic processes through a β-Arrestin1-ARHGAP21 complex. Here, we show that PTEN knockdown (KD) impairs β-Arrestin1 membrane localization, β-Arrestin1-ARHGAP21 interactions, Cdc42 activation, mitotic spindle orientation and 3D glandular morphogenesis. Effects of PTEN deficiency were phenocopied by β-Arrestin1 KD or inhibition of β-Arrestin1-ARHGAP21 interactions. Conversely, silencing of ARHGAP21 enhanced Cdc42 activation and rescued aberrant morphogenic processes of PTEN-deficient cultures. Expression of the PTEN C2 domain mimicked effects of full-length PTEN but a membrane-binding defective mutant of the C2 domain abrogated these properties. Our results show that PTEN controls multicellular assembly through a membrane-associated regulatory protein complex composed of β-Arrestin1, ARHGAP21 and Cdc42.

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Une nouvelle protéine RhoGAP impliquée dans la régulation du complexe Arp2/3 au niveau de l’appareil de Golgi : Un relais entre les protéines G ARF1 et Cdc42

Cited by 14 publications

References 17 publications

Analysis of Endocytic Pathways in Drosophila Cells Reveals a Conserved Role for GBF1 in Internalization via GEECs

Analysis of Endocytic Pathways in Drosophila Cells Reveals a Conserved Role for GBF1 in Internalization via GEECs

Distinct Transcriptional Signatures of Bone Marrow-Derived C57BL/6 and DBA/2 Dendritic Leucocytes Hosting Live Leishmania amazonensis Amastigotes

PTEN controls glandular morphogenesis through a juxtamembrane β-Arrestin1/ARHGAP21 scaffolding complex

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