Proteomic Analysis of Mammalian Primary Cilia
Open accessAbstract
The primary cilium is a microtubule-based organelle that senses extracellular signals as a cellular antenna. Primary cilia are found on many types of cells in our body and play important roles in development and physiology. Defects of primary cilia cause a broad class of human genetic diseases called ciliopathies. To gain new insights into ciliary functions and better understand the molecular mechanisms underlying ciliopathies, it is of high importance to generate a catalog of primary cilia proteins. In this study, we isolated primary cilia from mouse kidney cells by using a calcium-shock method and identified 195 candidate primary cilia proteins by MudPIT (multidimensional protein identification technology), protein correlation profiling, and subtractive proteomic analysis. Based on comparisons with other proteomic studies of cilia, around 75% of our candidate primary cilia proteins are shared components with motile or specialized sensory cilia. The remaining 25% of the candidate proteins are possible primary cilia-specific proteins. These possible primary cilia-specific proteins include EVC2, INPP5E, and inversin, several of which have been linked to known ciliopathies. We have performed the first reported proteomic analysis of primary cilia from mammalian cells. These results provide new insights into primary cilia structure and function.
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CFAP20 regulates ciliary movement (waveform) in Paramecium and Chlamydomonas.
“CFAP20 is a ciliopathy candidate known to modulate motile cilia in unicellular eukaryotes.”
From The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision (2022) · cites this paper as [18]
The Results section (‘Validation of Candidate Primary Cilia Proteins’; page unavailable) identifies Gtl3 as a homologue of Chlamydomonas BUG22 and reports its localization to mammalian primary cilia. Our copy does not say that this protein regulates ciliary movement or waveform in Paramecium or Chlamydomonas, or establish it as a ciliopathy candidate. (LLM, conf=0.82)
Experimental — accuracy not yet measuredA rare form of recessive inherited retinal dystrophy is attributed to variants in CFAP20.
“Here, we attribute a rare form of recessive inherited retinal dystrophy (IRD; a classic non-motile ciliopathy10,65,66) to variants in CFAP20, which encodes a remarkably conserved protein with well-established roles in motile cilia from diverse organisms15–18.”
From The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision (2022) · cites this paper as [18]
The Results section reports that Gtl3, a homologue of Chlamydomonas BUG22, localizes to primary cilia and nuclei. The Discussion names other genes associated with ciliopathies, but neither passage links CFAP20 variants to recessive inherited retinal dystrophy. The citing sentence presents that link as its authors’ own finding, not as a finding attributed to this source. (LLM, conf=0.78)
Experimental — accuracy not yet measuredCFAP20 might be generally required for regulating motile cilia function in diverse animals.
“Combined with sperm motility defects in Drosophila cfap20 mutants23, our findings suggest that CFAP20 might be generally required for regulating motile cilia function in diverse animals—as it does in the unicellular organisms Paramecium and Chlamydomonas15–18.”
From The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision (2022) · cites this paper as [18]
The Results (Validation of Candidate Primary Cilia Proteins; page unavailable) report that Gtl3, a homologue of Chlamydomonas BUG22, localizes to mammalian primary cilia. The Discussion (page unavailable) discusses proteins shared among cilia types, but neither passage addresses whether CFAP20 regulates motile-cilia function across animals. Searches for CFAP20, Drosophila sperm motility, Paramecium, and Chlamydomonas did not establish that claim. (LLM, conf=0.73)
Experimental — accuracy not yet measuredCFAP20 is present in photoreceptor and primary cilia proteomes.
“a notion supported by its presence not only in photoreceptor but also primary cilia proteomes18,53.”
From The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision (2022) · cites this paper as [18]
The Results section, ‘Validation of Candidate Primary Cilia Proteins’ (page unavailable), reports overlap between the primary-cilia candidate list and sensory-cilia proteomes, but does not identify CFAP20 among those proteins. Searches for ‘CFAP20’ and ‘FAP20’ found no passage establishing its presence in either proteome in our copy. (LLM, conf=0.72)
Experimental — accuracy not yet measured
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- Authors
- Ishikawa, H., Thompson, J., Yates, J. R., & Marshall, W. F.
- Affiliations
- University of California, San Francisco (US)
- Scripps Research Institute (US)
- Corresponding author
- Marshall, Wallace F.
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 22
- Issue
- 5
- Pages
- 414-419
- ISSN
- 0960-9822 (ISSN-L)
- PMC
- PMC3298568
- OpenAlex
- W2073521369
- Cited by
- 275
- References
- 39
- Citations by year
- 2026: 8 · 2025: 24 · 2024: 17 · 2023: 20 · 2022: 16 · 2021: 19 · 2020: 20 · 2019: 24 · 2018: 19 · 2017: 19 · 2016: 14 · 2015: 21 · 2014: 24 · 2013: 20 · 2012: 9
- FWCI
- 14.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 539 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (GM077004, P41 RR011823)
- W. M. Keck Foundation
- Japan Society for the Promotion of Science
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- primary cilia, ciliopathies, ciliary proteome, EVC2, INPP5E, inversin, mouse kidney cells, motile cilia, sensory cilia, subtractive proteomics
- MeSH terms
- Phosphoinositide 5-Phosphatases, Animals, Cilia, Kidney, Membrane Proteins, Phosphoric Monoester Hydrolases, Transcription Factors, Proteome, Intercellular Signaling Peptides and Proteins, Protein Array Analysis, Proteomics, Mice
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