Iryna M. Ethell
Assistant Professor
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Biomedical Research
Ph.D., 1991, Dnipropetrovsk National University, Ukraine
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Research Summary
Research in our laboratory focuses on studies of the molecular mechanisms that trigger dendritic spine formation. Dendritic spines are small protrusions on dendrites that serve as sites for excitatory synapses. Understanding the molecular basis of dendritic spine formation is fundamentally important to a variety of inherited developmental disorders associated with mental retardation and autism. Such disorders include Rett Syndrome, Down Syndrome, Angelman's Syndrome, and Fragile X Syndrome. Patients with these disorders exhibit malformation of dendritic spines. These abnormalities result in synaptic dysfunctions, mental retardation and autism. Recently, I have found that dendritic spine morphogenesis is controlled by the EphB-type receptor tyrosine kinases (Ethell et al., Neuron, 2001). Using GFP and recombinant DNAs in combinations with immunocytochemistry and confocal or two-photon microscopy, I have shown that EphB-type receptors regulate dendritic spine formation in cultured hippocampal neurons. Moreover, I have shown that EphB2 receptor phosphorylates and induces clustering of syndecan-2 (cell surface heparin sulfate proteoglycan) on postsynaptic membranes. Further, I have cloned novel synaptic syndecan-2 binding protein, synbindin that shares homology with proteins involved in vesicular transport and exocytosis. Our future research will focus on investigation of molecular mechanisms through which EphB receptors trigger spine mophogenesis. We will also study the role of synbindin in vesicular transport and exocytosis in dendritic spines using various molecular and cell biology tools.
Publications
I.M. Ethell, F. Irie, M.S. Kalo, J.R. Couchman, E.B. Pasquale and Y. Yamaguchi. 2001. EphB2/syndecan-2 signaling in dendritic spine morphogenesis. Neuron 31: 1001-1013.
R. Miura, I.M. Ethell and Y. Yamaguchi. 2001. Carbohydrate-protein interactions between HNK-1-reactive sulfoglucuronyl glycolipids and the proteoglycan lectin domain mediate neuronal cell adhesion and neurite outgrowth. J. Neurochem. 76: 413-424.
I.M. Ethell, K. Hagihara, Y. Miura, F. Irie and Y. Yamaguchi. 2000. Synbindin, a novel syndecan-2-binding protein in neuronal dendritic spines. J. Cell Biol. 151: 53-68.
A. Gartner, Y. Shostak, N. Hackel, I.M. Ethell and H. Thoenen. 2000. Ultrastructural identification of storage compartments and localization of activity-dependent secretion of neurotrophin 6 in hippocampal neurons. Mol. Cell. Neurosc. V. 15, p. 215-234.
I.M. Ethell and Y. Yamaguchi. 1999. Cell Surface Heparan Sulfate Proteoglycan Syndecan-2 Induces the Maturation of Dendritic Spines in Rat Hippocampal Neurons. J. Cell Biol. V. 144, p. 575-586.
H.-G. Wang, N. Pathan, I.M. Ethell, S. Krajewski, Y. Yamaguchi, F. Shibasaki, F. McKeon, T. Bobo, T.F. Franke and J. Reed. 1999. Ca-Induced apoptosis through calcineurin dephosphorylation of BAD. Science V. 284, p. 339-343.
R. Miura, A. Aspberg, I.M. Ethell, K. Hagihara, R.L. Schnaar, E. Ruoslahti and Y. Yamaguchi. 1999. The proteoglycan lectin domain binds sulfated cell surface glycolipids and supports cell adhesion and neurite outgrowth. J. Biol. Chem. V. 274, p. 11431-11437.
I.M. Krivko, D.J. Belliveau, J. Kohn, C. Lachance, C. Pozniak, D.A. Rusakov, D. Kaplan and F.D. Miller. 1997. NGF and Neurotrophin-3 both activate TrkA on Sympathetic Neurons but Differentially Regulate Survival and Neuritogenesis. J. Cell Biol. V. 136, p. 375-388.