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CEP128 Localizes to the Subdistal Appendages of the Mother Centriole and Regulates TGF-β/BMP Signaling at the Primary Cilium
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2018 (English)In: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 22, no 10, p. 2601-2614Article in journal (Refereed) Published
Abstract [en]

The centrosome is the main microtubule-organizing center in animal cells and comprises a mother and daughter centriole surrounded by pericentriolar material. During formation of primary cilia, the mother centriole transforms into a basal body that templates the ciliary axoneme. Ciliogenesis depends on mother centriole-specific distal appendages, whereas the role of subdistal appendages in ciliary function is unclear. Here, we identify CEP128 as a centriole subdistal appendage protein required for regulating ciliary signaling. Loss of CEP128 did not grossly affect centrosomal or ciliary structure but caused impaired transforming growth factor-β/bone morphogenetic protein (TGF-β/BMP) signaling in zebrafish and at the primary cilium in cultured mammalian cells. This phenotype is likely the result of defective vesicle trafficking at the cilium as ciliary localization of RAB11 was impaired upon loss of CEP128, and quantitative phosphoproteomics revealed that CEP128 loss affects TGF-β1-induced phosphorylation of multiple proteins that regulate cilium-associated vesicle trafficking. Mönnich et al. show that CEP128 localizes to the subdistal appendages of the mother centriole and basal body of the primary cilium. CEP128 regulates vesicular trafficking and targeting of RAB11 to the primary cilium. CEP128 loss leads to impaired TGF-β/BMP signaling, which, in zebrafish, is associated with defective organ development.

Place, publisher, year, edition, pages
Elsevier, 2018. Vol. 22, no 10, p. 2601-2614
Keyword [en]
basal body, BMP, bone morphogenetic protein, centriole, centrosome, CEP128, phosphoproteomics, primary cilium, subdistal appendage, TGF-β, transforming growth factor β, zebrafish
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Cell Biology
Identifiers
URN: urn:nbn:se:kth:diva-224560DOI: 10.1016/j.celrep.2018.02.043Scopus ID: 2-s2.0-85043371665OAI: oai:DiVA.org:kth-224560DiVA, id: diva2:1191776
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscienceNovo Nordisk
Note

QC 20180320

Available from: 2018-03-20 Created: 2018-03-20 Last updated: 2018-03-20Bibliographically approved

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Cellular and Clinical ProteomicsScience for Life Laboratory, SciLifeLab
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