TY - JOUR
T1 - Interactome analysis reveals that FAM161A, deficient in recessive retinitis pigmentosa, is a component of the Golgi-centrosomal network
AU - Di Gioia, Silvio Alessandro
AU - Farinelli, Pietro
AU - Letteboer, Stef J.F.
AU - Arsenijevic, Yvan
AU - Sharon, Dror
AU - Roepman, Ronald
AU - Rivolta, Carlo
N1 - Publisher Copyright:
© The Author 2015. Published by Oxford University Press. All rights reserved.
PY - 2015/1/18
Y1 - 2015/1/18
N2 - Defects in FAM161A, a protein of unknown function localized at the cilium of retinal photoreceptor cells, cause retinitis pigmentosa, a formof hereditary blindness. By using different fragments of this protein as baits to screen cDNAlibraries 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 Golgimaintenance, 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.
AB - Defects in FAM161A, a protein of unknown function localized at the cilium of retinal photoreceptor cells, cause retinitis pigmentosa, a formof hereditary blindness. By using different fragments of this protein as baits to screen cDNAlibraries 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 Golgimaintenance, 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.
UR - http://www.scopus.com/inward/record.url?scp=84930440766&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddv085
DO - 10.1093/hmg/ddv085
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C2 - 25749990
AN - SCOPUS:84930440766
SN - 0964-6906
VL - 24
SP - 3359
EP - 3371
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 12
M1 - ddv085
ER -