June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Tubby interacts with T-cell death associated gene 51 (TDAG51) in the mouse retina
Author Affiliations & Notes
  • Lorena Samentar
    School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States
    University of the Philippines in the Visayas, Iloilo, Philippines
  • Peipei Pan
    School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States
  • Josue Portillo
    School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States
  • Arnold Salazar
    School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States
  • Nora Blanca Caberoy
    School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States
    Nevada Institute of Personalized Medicine, University of Nevada Las Vegas, Las Vegas, Nevada, United States
  • Footnotes
    Commercial Relationships   Lorena Samentar, None; Peipei Pan, None; Josue Portillo, None; Arnold Salazar, None; Nora Caberoy, None
  • Footnotes
    Support  NEI K99/R00EY020865
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4519. doi:
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    • Get Citation

      Lorena Samentar, Peipei Pan, Josue Portillo, Arnold Salazar, Nora Blanca Caberoy; Tubby interacts with T-cell death associated gene 51 (TDAG51) in the mouse retina. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4519.

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

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Abstract

Purpose : Tubby mice with a spontaneous deletion of the C-terminal 44 amino acids exhibit progressive retinal and cochlear degeneration, and adult-onset obesity with undefined mechanisms. Using Open Reading Frame (ORF) phage display technology for protein-protein interactions, we identified TDAG51 (also known as pleckstrin homology-like domain family A member 1, PHLDA1) as a putative tubby-binding protein. The purpose of this study is to characterize the association of tubby with TDAG51 and define their roles in tubby-mediated disease pathogenesis.

Methods : TDAG51 was identified as a tubby-binding protein by ORF phage display. Expression of TDAG51 in mouse eye and brain was verified by reverse transcription-PCR (RT-PCR). Tubby-TDAG51 interaction was independently verified by in-vitro assays, e.g. co-immunoprecipitation and protein pull-down assays. The in vivo direct interactions between TDAG51 and tubby protein was characterized by fluorescence resonance energy transfer (FRET) analysis.

Results : TDAG51 is expressed in the mouse retina and brain. Protein pull-down assay demonstrated that it binds specifically to tubby N-terminal. TDAG51 was first identified as a pro-apoptotic gene in T-cell receptor-mediated cell death and is used as prognostic marker for breast cancer diagnosis. Its role in retinal homeostasis is not well established. Studies on subcellular localization and distribution of TDAG51 using immunohistochemical methods are currently underway.

Conclusions : The data revealed that TDAG51 specifically recognizes tubby N-terminal domain. The Tubby family of proteins are highly homologous in their C-terminal region, but diverse in the N-terminal half. Mutations in members of the family result to distinct disease profiles. Thus, their divergent N-termini may hold a key to elucidate the molecular mechanisms for different clinical manifestations. Understanding tubby-TDAG51 interaction will allow us to understand the role of tubby in retinal cell physiology and disease pathogenesis.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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