EHD2, EHD3, and EHD4 Encode Novel Members of a Highly Conserved Family of EH Domain-Containing Proteins

Pohl, Ute; Smith, Justin S.; Tachibana, Issei; Ueki, Keisuke; Lee, Hyun K.; Ramaswamy, Shivapriya; Wu, Qiang; Mohrenweiser, Harvey W.; Jenkins, Robert B.; Louis, David N.

doi:10.1006/geno.1999.6087

Cited by 82 publications

(88 citation statements)

References 28 publications

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“…1A). DNA sequences encoding this isoform, EHD2, were reported previously in the context of a genomics study without further characterization (28), and the murine homolog has not been identified previously.…”

Section: Identification Of Ehd2 In Membrane Fractions From 3t3-l1mentioning

confidence: 97%

“…Mouse EHD2 belongs to a group of four closely related proteins expressed in human cells that present a P-loop near the N terminus, followed by a coiled-coil region and an EH domain at the C terminus (28). This family of proteins has been suggested to function in endocytosis and membrane trafficking through binding of their EH domains to partner proteins with NPF motifs (29 -31).…”

Section: Identification Of Ehd2 In Membrane Fractions From 3t3-l1mentioning

confidence: 99%

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EHD2 and the Novel EH Domain Binding Protein EHBP1 Couple Endocytosis to the Actin Cytoskeleton

Guilherme

Soriano

Bose

et al. 2004

Journal of Biological Chemistry

138

181

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Here we identified two novel proteins denoted EH domain protein 2 (EHD2) and EHD2-binding protein 1 (EHBP1) that link clathrin-mediated endocytosis to the actin cytoskeleton. EHD2 contains an N-terminal P-loop and a C-terminal EH domain that interacts with NPF repeats in EHBP1. Disruption of EHD2 or EHBP1 function by small interfering RNA-mediated gene silencing inhibits endocytosis of transferrin into EEA1-positive endosomes as well as GLUT4 endocytosis into cultured adipocytes. EHD2 localizes with cortical actin filaments, whereas EHBP1 contains a putative actin-binding calponin homology domain. High expression of EHD2 or EHBP1 in intact cells mediates extensive actin reorganization. Thus EHD2 appears to connect endocytosis to the actin cytoskeleton through interactions of its N-terminal domain with membranes and its C-terminal EH domain with the novel EHBP1 protein.

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Section: Identification Of Ehd2 In Membrane Fractions From 3t3-l1mentioning

confidence: 97%

Section: Identification Of Ehd2 In Membrane Fractions From 3t3-l1mentioning

confidence: 99%

EHD2 and the Novel EH Domain Binding Protein EHBP1 Couple Endocytosis to the Actin Cytoskeleton

Guilherme

Soriano

Bose

et al. 2004

Journal of Biological Chemistry

138

181

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“…Multiple investigations have progressively narrowed the 19q common deletion region to an interval within the 19q13.3 cytogenetic band (120,(122)(123)(124), and several positional and/or functional candidates for the 19q tumor suppressor gene have been eliminated based on mutational analyses (125)(126)(127)(128)(129)(130). The 19q glioma tumor suppressor gene, however, remains to be identified.…”

Section: Chromosome Arm 19qmentioning

confidence: 99%

Genetic alterations in adult diffuse glioma: occurrence, significance, and prognostic implications

Smith

Jenkins²

2000

Front Biosci

144

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Our understanding of diffuse glioma development and progression has expanded remarkably over the past decade. As the genetic alterations responsible for these tumors are identified, molecular models of glioma pathogenesis are emerging and hold great promise to explain the biologic mechanisms of these neoplasms. Although these models continue to evolve and remain highly simplified, some of the genetic alterations that they encompass appear to be prognostically useful. Among the astrocytic gliomas, age and tumor grade are the most powerful indicators of patient survival, however, a wide range of variability remains, particularly among the lowgrade and anaplastic astrocytomas. Recent reports indicate that alterations of the PTEN tumor suppressor gene are independent predictors of overall survival for anaplastic astrocytoma patients, helping to distinguish the cases with behavior resembling their more malignant counterparts, the glioblastomas.Among the oligodendroglial tumors, alterations of the 1p and 19q chromosome arms have emerged as potentially powerful predictors of overall patient survival and in vivo chemotherapeutic response, while alterations of the p16/CDKN2A tumor suppressor gene suggest shorter overall survival. As our molecular models continue to improve, through functional analyses and the identification of additional genetic contributors, we will expand our capacity to more effectively prognose these patients and to design rational therapeutic strategies. INTRODUCTIONDiffuse gliomas exhibit an inherent tendency to progress to more malignant phenotypes and a broad range of clinical behavior. Classification of diffuse gliomas by histologic subtype (figure 1) and malignancy grade (figure 2),

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“…26). Unlike other mammalian EH domain-containing proteins, this subgroup of four homologous proteins has a single EH domain at its C terminus (27)(28)(29)(30), a central coiled-coil region involved in oligomerization (31)(32)(33), and an N-terminal regulatory region that binds to nucleotides (32,33). Emerging evidence has implicated all four C-terminal EHD proteins in the process of endocytosis (26).…”

mentioning

confidence: 99%

EHD1 and Eps15 Interact with Phosphatidylinositols via Their Eps15 Homology Domains

Naslavsky

Rahajeng

Chenavas

et al. 2007

Journal of Biological Chemistry

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The C-terminal Eps15 homology domain-containing protein, EHD1, regulates the recycling of receptors from the endocytic recycling compartment to the plasma membrane. In cells, EHD1 localizes to tubular and spherical recycling endosomes. To date, the mode by which EHD1 associates with endosomal membranes remains unknown, and it has not been determined whether this interaction is direct or via interacting proteins. Here, we provide evidence demonstrating that EHD1 has the ability to bind directly and preferentially to an array of phospholipids, preferring phosphatidylinositols with a phosphate at position 3. Previous studies have demonstrated that EH domains coordinate calcium binding and interact with proteins containing the tripeptide asparagine-proline-phenylalanine (NPF). Using two-dimensional nuclear magnetic resonance analysis, we now describe a new function for the Eps15 homology (EH) domain of EHD1 and show that it is capable of directly binding phosphatidylinositol moieties. Moreover, we have expanded our studies to include the C-terminal EH domain of EHD4 and the second of the three N-terminal EH domains of Eps15 and demonstrated that phosphatidylinositol binding may be a more general property shared by certain other EH domains. Further studies identified a positively charged lysine residue (Lys-483) localized within the third helix of the EH domain, on the opposite face of the NPF-binding pocket, as being critical for the interaction with the phosphatidylinositols.The internalization of receptors is a critical process for eukaryotic cells. Receptors can be internalized from the plasma membrane by a variety of well described mechanisms, including via clathrin-coated pits, independently of clathrin, and through caveolae (1). Once internalized, the small vesicles containing the internalized cargo fuse with early endosomes (also known as sorting endosomes), and the receptors are then either sent to late endosomes and on to the lysosomal pathway for degradation or recycled back to the plasma membrane, where they may participate in additional rounds of internalization (2). Receptor recycling occurs either directly from the sorting endosomes in a process known as "fast recycling" or indirectly in a process termed "slow" or "regulated" recycling (3). Slow recycling has been better characterized and traverses a complex series of tubular and vesicular membrane structures that emerge from the microtubule-organizing center and is collectively known as the endocytic recycling compartment (3, 4). Despite advances in recent years, the process of recycling is not as well understood as internalization.Among the key regulatory proteins that control endocytic transport and recycling are the Rab family of GTP-binding proteins (5-7). Over 60 different mammalian Rab proteins have been identified thus far, and their highly regulated GTP binding and subsequent hydrolysis lead to recruitment of a wide array of effector proteins that are important for vesicular transport and fusion processes within the endocytic pathways. For exa...

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EHD2, EHD3, and EHD4 Encode Novel Members of a Highly Conserved Family of EH Domain-Containing Proteins

Cited by 82 publications

References 28 publications

EHD2 and the Novel EH Domain Binding Protein EHBP1 Couple Endocytosis to the Actin Cytoskeleton

EHD2 and the Novel EH Domain Binding Protein EHBP1 Couple Endocytosis to the Actin Cytoskeleton

Genetic alterations in adult diffuse glioma: occurrence, significance, and prognostic implications

EHD1 and Eps15 Interact with Phosphatidylinositols via Their Eps15 Homology Domains

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