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A global analysis of IFT-A function reveals specialization for transport of membrane-associated proteins into cilia.
- Source :
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Journal of cell science [J Cell Sci] 2019 Feb 11; Vol. 132 (3). Date of Electronic Publication: 2019 Feb 11. - Publication Year :
- 2019
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Abstract
- Intraflagellar transport (IFT), which is essential for the formation and function of cilia in most organisms, is the trafficking of IFT trains (i.e. assemblies of IFT particles) that carry cargo within the cilium. Defects in IFT cause several human diseases. IFT trains contain the complexes IFT-A and IFT-B. To dissect the functions of these complexes, we studied a Chlamydomonas mutant that is null for the IFT-A protein IFT140. The mutation had no effect on IFT-B but destabilized IFT-A, preventing flagella assembly. Therefore, IFT-A assembly requires IFT140. Truncated IFT140, which lacks the N-terminal WD repeats of the protein, partially rescued IFT and supported formation of half-length flagella that contained normal levels of IFT-B but greatly reduced amounts of IFT-A. The axonemes of these flagella had normal ultrastructure and, as investigated by SDS-PAGE, normal composition. However, composition of the flagellar 'membrane+matrix' was abnormal. Analysis of the latter fraction by mass spectrometry revealed decreases in small GTPases, lipid-anchored proteins and cell signaling proteins. Thus, IFT-A is specialized for the import of membrane-associated proteins. Abnormal levels of the latter are likely to account for the multiple phenotypes of patients with defects in IFT140.This article has an associated First Person interview with the first author of the paper.<br />Competing Interests: Competing interestsThe authors declare no competing or financial interests.<br /> (© 2019. Published by The Company of Biologists Ltd.)
- Subjects :
- Algal Proteins chemistry
Algal Proteins metabolism
Axoneme metabolism
Axoneme ultrastructure
Carrier Proteins chemistry
Carrier Proteins genetics
Carrier Proteins metabolism
Cell Membrane ultrastructure
Cerebellar Ataxia genetics
Cerebellar Ataxia metabolism
Cerebellar Ataxia pathology
Chlamydomonas reinhardtii metabolism
Chlamydomonas reinhardtii ultrastructure
Cilia ultrastructure
Ellis-Van Creveld Syndrome genetics
Ellis-Van Creveld Syndrome metabolism
Ellis-Van Creveld Syndrome pathology
Flagella ultrastructure
Gene Expression
Genes, Reporter
Green Fluorescent Proteins genetics
Green Fluorescent Proteins metabolism
Humans
Lipid-Linked Proteins metabolism
Luminescent Proteins genetics
Luminescent Proteins metabolism
Monomeric GTP-Binding Proteins genetics
Monomeric GTP-Binding Proteins metabolism
Mutation
Organisms, Genetically Modified
Protein Transport
Retinitis Pigmentosa genetics
Retinitis Pigmentosa metabolism
Retinitis Pigmentosa pathology
Signal Transduction
Red Fluorescent Protein
Algal Proteins genetics
Cell Membrane metabolism
Chlamydomonas reinhardtii genetics
Cilia metabolism
Flagella metabolism
Lipid-Linked Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9137
- Volume :
- 132
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of cell science
- Publication Type :
- Academic Journal
- Accession number :
- 30659111
- Full Text :
- https://doi.org/10.1242/jcs.220749