Interactome analysis reveals that FAM161A, deficient in recessive retinitis pigmentosa, is a component of the Golgi-centrosomal network
| Autor: | Pietro Farinelli, Yvan Arsenijevic, Stef J.F. Letteboer, Carlo Rivolta, Dror Sharon, Ronald Roepman, Silvio Alessandro Di Gioia |
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| Rok vydání: | 2015 |
| Předmět: |
Intracellular Space
Golgi Apparatus Genes Recessive Ciliary basal body Biology Interactome Cell Line symbols.namesake Microtubule Two-Hybrid System Techniques Protein Interaction Mapping Retinitis pigmentosa Genetics medicine Animals Humans Protein Interaction Maps Eye Proteins Molecular Biology Cytoskeleton Genetics (clinical) Centrosome Cilium General Medicine Golgi apparatus medicine.disease Cell biology Transport protein Protein Transport Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] symbols Cattle Carrier Proteins Retinitis Pigmentosa Protein Binding |
| Zdroj: | Human Molecular Genetics, 24, 3359-71 Human Molecular Genetics, 24, 12, pp. 3359-71 Human molecular genetics Human Molecular Genetics, vol. 24, no. 12, pp. 3359-3371 |
| ISSN: | 0964-6906 |
| Popis: | Item does not contain fulltext Defects in FAM161A, a protein of unknown function localized at the cilium of retinal photoreceptor cells, cause retinitis pigmentosa, a form of hereditary blindness. By using different fragments of this protein as baits to screen cDNA libraries of human and bovine retinas, we defined a yeast two-hybrid-based FAM161A interactome, identifying 53 bona fide partners. In addition to statistically significant enrichment in ciliary proteins, as expected, this interactome revealed a substantial bias towards proteins from the Golgi apparatus, the centrosome and the microtubule network. Validation of interaction with key partners by co-immunoprecipitation and proximity ligation assay confirmed that FAM161A is a member of the recently recognized Golgi-centrosomal interactome, a network of proteins interconnecting Golgi maintenance, intracellular transport and centrosome organization. Notable FAM161A interactors included AKAP9, FIP3, GOLGA3, KIFC3, KLC2, PDE4DIP, NIN and TRIP11. Furthermore, analysis of FAM161A localization during the cell cycle revealed that this protein followed the centrosome during all stages of mitosis, likely reflecting a specific compartmentalization related to its role at the ciliary basal body during the G0 phase. Altogether, these findings suggest that FAM161A's activities are probably not limited to ciliary tasks but also extend to more general cellular functions, highlighting possible novel mechanisms for the molecular pathology of retinal disease. |
| Databáze: | OpenAIRE |
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