Identification of potential mediators of retinotopic mapping: A comparative proteomic analysis of optic nerve from WT and Phr1 retinal knockout mice

Andrew R. Lee, Rachel R. Lamb, Julietta H. Chang, Petra Erdmann-Gilmore, Cheryl F. Lichti, Henry W. Rohrs, James P. Malone, Yogesh P. Wairkar, Aaron Diantonio, R. Reid Townsend, Susan M. Culican

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Retinal ganglion cells (RGCs) transmit visual information topographically from the eye to the brain, creating a map of visual space in retino-recipient nuclei (retinotopy). This process is affected by retinal activity and by activity-independent molecular cues. Phr1, which encodes a presumed E3 ubiquitin ligase (PHR1), is required presynaptically for proper placement of RGC axons in the lateral geniculate nucleus and the superior colliculus, suggesting that increased levels of PHR1 target proteins may be instructive for retinotopic mapping of retinofugal projections. To identify potential target proteins, we conducted a proteomic analysis of optic nerve to identify differentially abundant proteins in the presence or absence of Phr1 in RGCs. 1D gel electrophoresis identified a specific band in controls that was absent in mutants. Targeted proteomic analysis of this band demonstrated the presence of PHR1. Additionally, we conducted an unbiased proteomic analysis that identified 30 proteins as being significantly different between the two genotypes. One of these, heterogeneous nuclear ribonucleoprotein M (hnRNP-M), regulates antero-posterior patterning in invertebrates and can function as a cell surface adhesion receptor in vertebrates. Thus, we have demonstrated that network analysis of quantitative proteomic data is a useful approach for hypothesis generation and for identifying biologically relevant targets in genetically altered biological models.

Original languageEnglish (US)
Pages (from-to)5515-5526
Number of pages12
JournalJournal of Proteome Research
Volume11
Issue number11
DOIs
StatePublished - Nov 2 2012

Keywords

  • LC-MS
  • Mycbp2
  • Phr1
  • hnRNP-M
  • label-free quantitative proteomics
  • network analysis
  • proteomics
  • retinal ganglion cell
  • retinotopy
  • ubiquitin ligase

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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    Lee, A. R., Lamb, R. R., Chang, J. H., Erdmann-Gilmore, P., Lichti, C. F., Rohrs, H. W., Malone, J. P., Wairkar, Y. P., Diantonio, A., Townsend, R. R., & Culican, S. M. (2012). Identification of potential mediators of retinotopic mapping: A comparative proteomic analysis of optic nerve from WT and Phr1 retinal knockout mice. Journal of Proteome Research, 11(11), 5515-5526. https://doi.org/10.1021/pr300767a