title: Identification of potential mediators of retinotopic mapping: a comparative proteomic analysis of optic nerve from WT and Phr1 retinal knockout mice.
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.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Lee
authors.forename: Rachel R
authors.initials: RR
authors.lastname: Lamb
authors.forename: Julietta H
authors.initials: JH
authors.lastname: Chang
authors.forename: Petra
authors.initials: P
authors.lastname: Erdmann-Gilmore
authors.forename: Cheryl F
authors.initials: CF
authors.lastname: Lichti
authors.forename: Henry W
authors.initials: HW
authors.lastname: Rohrs
authors.forename: James P
authors.initials: JP
authors.lastname: Malone
authors.forename: Yogesh P
authors.initials: YP
authors.lastname: Wairkar
authors.forename: Aaron
authors.initials: A
authors.lastname: DiAntonio
authors.forename: R Reid
authors.initials: RR
authors.lastname: Townsend
authors.forename: Susan M
authors.initials: SM
authors.lastname: Culican
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002853:Chromatography, Liquid; D015342:DNA Probes; D004591:Electrophoresis, Polyacrylamide Gel; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D013058:Mass Spectrometry; D051379:Mice; D018345:Mice, Knockout; D009900:Optic Nerve / Q000378:metabolism*; D020543:Proteome; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases
chemical_list: D002352:Carrier Proteins; D015342:DNA Probes; D020543:Proteome; C532954:Mycbp2 protein, mouse; D044767:Ubiquitin-Protein Ligases