Vesicular transport is essential for delivering cargo to intracellular destinations. Evi5 is a Rab11-GTPase-activating protein involved in endosome recycling. In humans, Evi5 is a high-risk locus for multiple sclerosis, a debilitating disease that also presents with excess iron in the CNS. In insects, the prothoracic gland (PG) requires entry of extracellular iron to synthesize steroidogenic enzyme cofactors. The mechanism of peripheral iron uptake in insect cells remains controversial. We show that Evi5-depletion in the Drosophila PG affected vesicle morphology and density, blocked endosome recycling and impaired trafficking of transferrin-1, thus disrupting heme synthesis due to reduced cellular iron concentrations. We show that ferritin delivers iron to the PG as well, and interacts physically with Evi5. Further, ferritin-injection rescued developmental delays associated with Evi5-depletion. To summarize, our findings show that Evi5 is critical for intracellular iron trafficking via transferrin-1 and ferritin, and implicate altered iron homeostasis in the etiology of multiple sclerosis.
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Drosophila Evi5 is a critical regulator of intracellular iron transport via transferrin and ferritin interactions.
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University of Alberta, Faculty of Science, Edmonton, Alberta, T6G 2E9, Canada.
Vesicular transport is essential for delivering cargo to intracellular destinations. Evi5 is a Rab11-GTPase-activating protein involved in endosome recycling. In humans, Evi5 is a high-risk locus for multiple sclerosis, a debilitating disease that also presents with excess iron in the CNS.
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Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, Research Center for Translational Medicine Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Amphibians such as salamanders and the African clawed frog are great models for regeneration studies because they can fully regenerate their lost organs. While axolotl can regenerate damaged organs throughout its lifetime, has a limited regeneration capacity after metamorphosis. The ecotropic viral integrative factor 5 (Evi5) is of great interest because its expression is highly upregulated in the limb blastema of axolotls, but remains unchanged in the fibroblastema of post-metamorphic frogs.
View Article and Find Full Text PDFGenome-wide association study revealed novel candidate gene loci associated with soluble E-selectin levels in a Taiwanese population.
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Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; The Division of Cardiology, Department of Internal Medicine and Cardiovascular Center, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan. Electronic address:
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- The study investigates genetic factors that influence levels of soluble E-selectin (sE-selectin), which are linked to inflammation and cardiometabolic disorders, using data from the Taiwan Biobank.
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The Evi5 oncogene promotes laryngeal cancer cells proliferation by stabilizing c-Myc protein.
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3Department of Oncology, Affiliated Dongfeng Hospital, Hubei University of Medicine, No. 10, Daling Road, Shiyan, 442008 Hubei People's Republic of China.
Background: The Ecotropic viral integration site 5 (Evi5) is recognized as a potential oncogene and a cell cycle regulator. Evi5 regulates the abundance of Emi1, an inhibitor of the anaphase-promoting complex/cyclosome, to govern mitotic fidelity. Evi5 has been shown to be dysregulated in several cancer types.
View Article and Find Full Text PDFIdentification of Rab11 as a small GTPase binding protein for the Evi5 oncogene.
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Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
The Evi5 oncogene has recently been shown to regulate the stability and accumulation of critical G(1) cell cycle factors including Emi1, an inhibitor of the anaphase-promoting complex/cyclosome, and cyclin A. Sequence analysis of the amino terminus of Evi5 reveals a Tre-2, Bub2, Cdc16 domain, which has been shown to be a binding partner and GTPase-activating protein domain for the Rab family of small Ras-like GTPases. Here we describe the identification of Evi5 as a candidate binding protein for Rab11, a GTPase that regulates intracellular transport and has specific roles in endosome recycling and cytokinesis.
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