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 Wairkar, Aaron Diantonio, R. Reid Townsend, Susan M. Culican

Research output: Contribution to journalArticle

1 Citation (Scopus)

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

Fingerprint

Optic Nerve
Knockout Mice
Proteomics
Retinal Ganglion Cells
Optics
Heterogeneous-Nuclear Ribonucleoprotein Group M
Proteins
Geniculate Bodies
Biological Models
Ubiquitin-Protein Ligases
Superior Colliculi
Cell Surface Receptors
Invertebrates
Electric network analysis
Electrophoresis
Cell Adhesion
Cues
Axons
Vertebrates
Brain

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Identification of potential mediators of retinotopic mapping : A comparative proteomic analysis of optic nerve from WT and Phr1 retinal knockout mice. / Lee, Andrew R.; Lamb, Rachel R.; Chang, Julietta H.; Erdmann-Gilmore, Petra; Lichti, Cheryl F.; Rohrs, Henry W.; Malone, James P.; Wairkar, Yogesh; Diantonio, Aaron; Townsend, R. Reid; Culican, Susan M.

In: Journal of Proteome Research, Vol. 11, No. 11, 02.11.2012, p. 5515-5526.

Research output: Contribution to journalArticle

Lee, AR, Lamb, RR, Chang, JH, Erdmann-Gilmore, P, Lichti, CF, Rohrs, HW, Malone, JP, Wairkar, Y, Diantonio, A, Townsend, RR & Culican, SM 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, vol. 11, no. 11, pp. 5515-5526. https://doi.org/10.1021/pr300767a
Lee, Andrew R. ; Lamb, Rachel R. ; Chang, Julietta H. ; Erdmann-Gilmore, Petra ; Lichti, Cheryl F. ; Rohrs, Henry W. ; Malone, James P. ; Wairkar, Yogesh ; Diantonio, Aaron ; Townsend, R. Reid ; Culican, Susan M. / Identification of potential mediators of retinotopic mapping : A comparative proteomic analysis of optic nerve from WT and Phr1 retinal knockout mice. In: Journal of Proteome Research. 2012 ; Vol. 11, No. 11. pp. 5515-5526.
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AU - Erdmann-Gilmore, Petra

AU - Lichti, Cheryl F.

AU - Rohrs, Henry W.

AU - Malone, James P.

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AU - Townsend, R. Reid

AU - Culican, Susan M.

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