ArticleThe Journal of biological chemistry2011
Kinetic studies of the Arf activator Arno on model membranes in the presence of Arf effectors suggest control by a positive feedback loop.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 73 citations in OpenAlex.
- The Abl-interactor Abi suppresses the function of the BRAG2 GEF family member Schizo.Biology open · 2024Article
- AMPK promotes Arf6 activation in a kinase-independent manner upon glucose starvation.Journal of cell science · 2022Article
- Physiological and Pathological Roles of the Cytohesin Family in Neurons.International journal of molecular sciences · 2022Review
- Article
- Stochasticity and positive feedback enable enzyme kinetics at the membrane to sense reaction size.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Extensive GTPase crosstalk regulates Golgi trafficking and maturation.Current opinion in cell biology · 2020Review
- The C-terminal domain of EFA6A interacts directly with F-actin and assembles F-actin bundles.Scientific reports · 2019Article
- Structural Organization and Dynamics of Homodimeric Cytohesin Family Arf GTPase Exchange Factors in Solution and on Membranes.Structure (London, England : 1993) · 2019Article
- Macropinosome formation, maturation and membrane recycling: lessons from clathrin-independent endosomal membrane systems.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019Article
- Autoactivation of small GTPases by the GEF-effector positive feedback modules.F1000Research · 2019Review
- Article
- ARF1 and ARF6 regulate recycling of GRASP/Tamalin and the Rac1-GEF Dock180 during HGF-induced Rac1 activation.Small GTPases · 2018Article
- The Arf-GDP-regulated recruitment of GBF1 to Golgi membranes requires domains HDS1 and HDS2 and a Golgi-localized protein receptor.Journal of cell science · 2018Article
- The ARF guanine nucleotide exchange factor GBF1 is targeted to Golgi membranes through a PIP-binding domain.Journal of cell science · 2018Article
- Structural Dynamics Control Allosteric Activation of Cytohesin Family Arf GTPase Exchange Factors.Structure (London, England : 1993) · 2018Article
- Multiple interactions between an Arf/GEF complex and charged lipids determine activation kinetics on the membrane.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Article
- Inhibition of WAVE Regulatory Complex Activation by a Bacterial Virulence Effector Counteracts Pathogen Phagocytosis.Cell reports · 2016Article
- Allosteric regulation of Arf GTPases and their GEFs at the membrane interface.Small GTPases · 2016Review
- ARF-GEF cytohesin-2/ARNO regulates R-Ras and α5-integrin recycling through an EHD1-positive compartment.Molecular biology of the cell · 2015Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteins of the cytohesin/Arno/Grp1 family of Arf activators are positive regulators of the insulin-signaling pathway and control various remodeling events at the plasma membrane. Arno has a catalytic Sec7 domain, which promotes GDP to GTP exchange on Arf, followed by a pleckstrin homology (PH) domain. Previous studies have revealed two functions of the PH domain: inhibition of the Sec7 domain and membrane targeting. Interestingly, the Arno PH domain interacts not only with a phosphoinositide (phosphatidylinositol 4,5-bisphosphate or phosphatidylinositol 3,4,5-trisphosphate) but also with an activating Arf family member, such as Arf6 or Arl4. Using the full-length membrane-bound forms of Arf1 and Arf6 instead of soluble forms, we show here that the membrane environment dramatically affects the mechanism of Arno activation. First, Arf6-GTP stimulates Arno at nanomolar concentrations on liposomes compared with micromolar concentrations in solution. Second, mutations in the PH domain that abolish interaction with Arf6-GTP render Arno completely inactive when exchange reactions are reconstituted on liposomes but have no effect on Arno activity in solution. Third, Arno is activated by its own product Arf1-GTP in addition to a distinct activating Arf isoform. Consequently, Arno activity is strongly modulated by competition with Arf effectors. These results show that Arno behaves as a bistable switch, having an absolute requirement for activation by an Arf protein but, once triggered, becoming highly active through the positive feedback effect of Arf1-GTP. This property of Arno might provide an explanation for its function in signaling pathways that, once triggered, must move forward decisively.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.