The proteome of the mouse photoreceptor sensory cilium complex

Qin Liu, Glenn Tan, Natasha Levenkova, Tiansen Li, Edward N Pugh Jr, John J. Rux, David W. Speichers, Eric A. Pierce

Research output: Contribution to journalArticle

235 Citations (Scopus)

Abstract

Primary cilia play critical roles in many aspects of biology. Specialized versions of primary cilia are involved in many aspects of sensation. The single photoreceptor sensory cilium (PSC) or outer segment elaborated by each rod and cone photoreceptor cell of the retina is a classic example. Mutations in genes that encode cilia components are common causes of disease, including retinal degenerations. The protein components of mammalian primary and sensory cilia have not been defined previously. Here we report a detailed proteomics analysis of the mouse PSC complex. The PSC complex comprises the outer segment and its cytoskeleton, including the axoneme, basal body, and ciliary rootlet, which extends into the inner segment of photoreceptor cells. The PSC complex proteome contains 1968 proteins represented by three or more unique peptides, including ∼1500 proteins not detected in cilia from lower organisms. This includes 105 hypothetical proteins and 60 proteins encoded by genes that map within the critical intervals for 23 inherited cilia-related disorders, increasing their priority as candidate genes. The PSC complex proteome also contains many cilia proteins not identified previously in photoreceptors, including 13 proteins produced by genes that harbor mutations that cause cilia disease and seven intraflagellar transport proteins. Analyses of PSC complexes from rootletin knockout mice, which lack ciliary rootlets, confirmed that 1185 of the identified PSC complex proteins are derived from the outer segment. The mass spectrometry data, bench-marked by 15 well characterized outer segment proteins, were used to quantify the copy number of each protein in a mouse rod outer segment. These results reveal mammalian cilia to be several times more complex than the cilia of unicellular organisms and open novel avenues for studies of how cilia are built and maintained and how these processes are disrupted in human disease.

Original languageEnglish (US)
Pages (from-to)1299-1317
Number of pages19
JournalMolecular and Cellular Proteomics
Volume6
Issue number8
DOIs
StatePublished - Aug 2007
Externally publishedYes

Fingerprint

Cilia
Proteome
Proteins
Genes
Ports and harbors
Mass spectrometry
Cones
Carrier Proteins
Basal Bodies
Axoneme
Retinal Cone Photoreceptor Cells
Rod Cell Outer Segment
Retinal Rod Photoreceptor Cells
Photoreceptor Cells
Retinal Degeneration
Mutation
Vertebrate Photoreceptor Cells
Peptides

ASJC Scopus subject areas

  • Biochemistry

Cite this

The proteome of the mouse photoreceptor sensory cilium complex. / Liu, Qin; Tan, Glenn; Levenkova, Natasha; Li, Tiansen; Pugh Jr, Edward N; Rux, John J.; Speichers, David W.; Pierce, Eric A.

In: Molecular and Cellular Proteomics, Vol. 6, No. 8, 08.2007, p. 1299-1317.

Research output: Contribution to journalArticle

Liu, Q, Tan, G, Levenkova, N, Li, T, Pugh Jr, EN, Rux, JJ, Speichers, DW & Pierce, EA 2007, 'The proteome of the mouse photoreceptor sensory cilium complex', Molecular and Cellular Proteomics, vol. 6, no. 8, pp. 1299-1317. https://doi.org/10.1074/mcp.M700054-MCP200
Liu, Qin ; Tan, Glenn ; Levenkova, Natasha ; Li, Tiansen ; Pugh Jr, Edward N ; Rux, John J. ; Speichers, David W. ; Pierce, Eric A. / The proteome of the mouse photoreceptor sensory cilium complex. In: Molecular and Cellular Proteomics. 2007 ; Vol. 6, No. 8. pp. 1299-1317.
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