ArticleThe Journal of biological chemistry2016
EHD3 Protein Is Required for Tubular Recycling Endosome Stabilization, and an Asparagine-Glutamic Acid Residue Pair within Its Eps15 Homology (EH) Domain Dictates Its Selective Binding to NPF Peptides.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- A Quarter Century of EHD Protein Research: From Endosomal Recycling to Ciliopathies.Traffic (Copenhagen, Denmark) · 2026Review
- The endocytic fission protein EHD1 interacts with tubulin and regulates microtubule function.Biochimica et biophysica acta. Molecular cell research · 2026Article
- Revealing sphingolipid metabolism genes as biomarkers for the diagnosis of invasive pituitary adenomas in silico and in vivo.European journal of medical research · 2025Article
- RREB1 regulates neuronal proteostasis and the microtubule network.Science advances · 2024Article
- ZebrafishFrontiers in molecular neuroscience · 2024Article
- Differential requirements for the Eps15 homology domain proteins EHD4 and EHD2 in the regulation of mammalian ciliogenesis.Traffic (Copenhagen, Denmark) · 2022Article
- Functional and behavioral effects of de novo mutations in calcium-related genes in patients with bipolar disorder.Human molecular genetics · 2021Article
- A junctional PACSIN2/EHD4/MICAL-L1 complex coordinates VE-cadherin trafficking for endothelial migration and angiogenesis.Nature communications · 2021Article
- Temporal Quantitative Profiling of Newly Synthesized Proteins during Aβ Accumulation.Journal of proteome research · 2021Article
- Entacapone Treatment Modulates Hippocampal Proteins Related to Synaptic Vehicle Trafficking.Cells · 2020Article
- A semi-supervised Bayesian approach for simultaneous protein sub-cellular localisation assignment and novelty detection.PLoS computational biology · 2020Article
- An early endosome-derived retrograde trafficking pathway promotes secretory granule maturation.The Journal of cell biology · 2020Article
- DDHD1, but Not DDHD2, Suppresses Neurite Outgrowth in SH-SY5Y and PC12 Cells by Regulating Protein Transport From Recycling Endosomes.Frontiers in cell and developmental biology · 2020Article
- Article
- Rab22A recruits BLOC-1 and BLOC-2 to promote the biogenesis of recycling endosomes.EMBO reports · 2018Article
- Article
- The enigmatic endosome - sorting the ins and outs of endocytic trafficking.Journal of cell science · 2018Review
- Extracellular Vesicle Subtypes Released From Activated or Apoptotic T-Lymphocytes Carry a Specific and Stimulus-Dependent Protein Cargo.Frontiers in immunology · 2018Article
- EHD Proteins Cooperate to Generate Caveolar Clusters and to Maintain Caveolae during Repeated Mechanical Stress.Current biology : CB · 2017Article
- Regulated methionine oxidation by monooxygenases.Free radical biology & medicine · 2017Review
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6 authors.
Funding
Abstract
An elaborate network of dynamic lipid membranes, termed tubular recycling endosomes (TRE), coordinates the process of endocytic recycling in mammalian cells. The C-terminal Eps15 homology domain (EHD)-containing proteins have been implicated in the bending and fission of TRE, thus regulating endocytic recycling. EHD proteins have an EH domain that interacts with proteins containing an NPF motif. We found that NPF-containing EHD1 interaction partners such as molecules interacting with CasL-like1 (MICAL-L1) and Syndapin2 are essential for TRE biogenesis. Also crucial for TRE biogenesis is the generation of phosphatidic acid, an essential lipid component of TRE that serves as a docking point for MICAL-L1 and Syndapin2. EHD1 and EHD3 have 86% amino acid identity; they homo- and heterodimerize and partially co-localize to TRE. Despite their remarkable identity, they have distinct mechanistic functions. EHD1 induces membrane vesiculation, whereas EHD3 supports TRE biogenesis and/or stabilization by an unknown mechanism. While using phospholipase D inhibitors (which block the conversion of glycerophospholipids to phosphatidic acid) to deplete cellular TRE, we observed that, upon inhibitor washout, there was a rapid and dramatic regeneration of MICAL-L1-marked TRE. Using this "synchronized" TRE biogenesis system, we determined that EHD3 is involved in the stabilization of TRE rather than in their biogenesis. Moreover, we identify the residues Ala-519/Asp-520 of EHD1 and Asn-519/Glu-520 of EHD3 as defining the selectivity of these two paralogs for NPF-containing binding partners, and we present a model to explain the atomic mechanism and provide new insight for their differential roles in vesiculation and tubulation, respectively.
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