May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
Interaction Between Myocilin and Gamma–Synuclein
Author Affiliations & Notes
  • A.P. Surguchov
    Neurology, Kansas University Medical Center, Kansas City, KS
  • B.C. Park
    Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL
  • B.Y. J. T. Yue
    Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL
  • S.I. Tomarev
    Laboratory of Molecular and Developmental Biology, National Eye Institute, Bethesda, MD
  • I.G. Surgucheva
    Neurology, Kansas University Medical Center, Kansas City, KS
  • Footnotes
    Commercial Relationships  A.P. Surguchov, None; B.C. Park, None; B.Y.J.T. Yue, None; S.I. Tomarev, None; I.G. Surgucheva, None.
  • Footnotes
    Support  NIH grants EY13784–03; EY05628 and EY01792 (core);
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 1347. doi:
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      A.P. Surguchov, B.C. Park, B.Y. J. T. Yue, S.I. Tomarev, I.G. Surgucheva; Interaction Between Myocilin and Gamma–Synuclein . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1347.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose:Myocilin (MYOC) is a protein of unknown function that has been linked to glaucoma. MYOC is both intra– and extracellular glycoprotein produced in TM and other ocular and nonocular tissues that forms dimers and oligomers. The majority of MYOC mutants with point substitutions is not secreted from cells and can significantly inhibit secretion of wild–type protein when the two forms are co–expressed. The purpose of this study is to identify MYOC–binding proteins and analyze which MYOC properties are modified after such interaction. Methods:Immunoprecipitation, pull down and overlay experiments were used together with Western blotting assays and overexpression of recombinant proteins in trabecular meshwork cells, retinal ganglion cells and hippocampal neuron cultures. Results:MYOC interacts with a member of the synuclein family, γ–synuclein according to the results of immunoprecipitation and pull down experiments. Earlier we found that γ–synuclein is implicated in glaucomatous alterations in the optic nerve. (J. Neuroscience.Res, 2002,68,97–106)). In addition, γ–synuclein upregulates MYOC expression, inhibits its secretion and prevents the formation of higher molecular weight aggregates in different types of cultured cells of both ocular and non–ocular origin. γ–Synuclein is expressed in retinal ganglion cells (RGC), trabecular meshwork (TM) and glial cells of the optic nerve. Immunocytochemical staining demonstrated partial overlapping of MYOC and γ–synuclein localization. According to overlay data, γ–synuclein interacts with C–terminal fragment of MYOC. These results are in good agreement with the lack of γ–synuclein effect on secretion of Gln368Stop mutant. Conclusions: The influence of γ–synuclein on MYOC secretion mimics the effect of some mutant forms of MYOC associated with POAG, since the presence of the mutated MYOC appears to suppress secretion of the normal protein. These results suggest a possible role of γ–synuclein– MYOC interactions in the pathogenesis of glaucoma.

Keywords: trabecular meshwork • ganglion cells • protein structure/function 
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