April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Set-β Modulates Neurite Growth In Retinal Ganglion Cells In Opposite Ways, Depending On Its Subcellular Localization
Author Affiliations & Notes
  • Ephraim C. Trakhtenberg
    Ophthalmology, Neuroscience Program, Univ. of Miami, Bascom Palmer Eye Inst, Miami, Florida
  • Steven Yang
    Univ. of Miami Miller Sch. of Med, Miami, Florida
  • Yan Wang
    Ophthalmology, Univ. of Miami; Bascom Palmer Eye Inst, Miami, Florida
  • Jeffrey L. Goldberg
    Ophthalmology, Neuroscience Program, Univ. of Miami, Bascom Palmer Eye Inst, Miami, Florida
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 434. doi:
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      Ephraim C. Trakhtenberg, Steven Yang, Yan Wang, Jeffrey L. Goldberg; Set-β Modulates Neurite Growth In Retinal Ganglion Cells In Opposite Ways, Depending On Its Subcellular Localization. Invest. Ophthalmol. Vis. Sci. 2011;52(14):434.

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

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Abstract

Purpose: : Adult mammalian central nervous system (CNS) axons are unable to regrow their axons after injury, but immature CNS axons grow robustly. Manipulation of various cell-autonomous factors along with overcoming the inhibitory adult CNS environment only partially restores regeneration. Recent evidence suggests that postnatally, CNS neurons themselves decrease their intrinsic regenerative capacity. Our lab‘s microarray analysis showed Set-β oncogene expression to be developmentally downregulated in retinal ganglion cells (RGC; a type of CNS neuron), around birth, when axon growth slows. Also known as a template-activating factor (TAF)-I, Set-β localizes to the nucleus and modulates transcription, but truncated TAF-Iβ isoform can function in the cytoplasm.

Methods: : Set-β, myristoylated (myr)-Set-β, and mCherry were overexpressed in purified P3 RGCs, incubated for 24 hours, immunostained with transfection and neurite markers, and imaged. Neurite length was quantified using ImageJ Plugin, Neurite Tracer. Data was analyzed with SPSS, ANOVA with post hoc Dunnett’s test.

Results: : We found that Set-β overexpressed in RGCs localizes to the nucleus and suppresses neurite growth, while myristoylated-Set-β remains partially in the cytoplasm and increases neurite growth.

Conclusions: : We hypothesize that Set-β suppresses neurite growth by modulating activities of the Krüppel-like family transcription factors, while it promotes neurite growth through its activity in the cytoplasm and the neurites by activating Rac family of small GTPases, particularly Rac1 and -3.

Keywords: optic nerve • regeneration • retina: proximal (bipolar, amacrine, and ganglion cells) 
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