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Cell Rep. 2018 Mar 6;22(10):2584-2592. doi: 10.1016/j.celrep.2018.02.043.

CEP128 Localizes to the Subdistal Appendages of the Mother Centriole and Regulates TGF-β/BMP Signaling at the Primary Cilium.

Author information

1
Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark.
2
Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark.
3
Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark; Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
4
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
5
Cell Biology/Electron Microscopy, University of Bayreuth, Universitaetsstrasse 30, 95440 Bayreuth, Germany.
6
Science for Life Laboratory, School of Biotechnology, KTH Royal Institute of Technology, SE-171 21 Stockholm, Sweden.
7
Cell Biology/Electron Microscopy, University of Bayreuth, Universitaetsstrasse 30, 95440 Bayreuth, Germany. Electronic address: stefan.geimer@uni-bayreuth.de.
8
Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark. Electronic address: stchristensen@bio.ku.dk.
9
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark. Electronic address: jens.andersen@bmb.sdu.dk.
10
Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark. Electronic address: larsal@sund.ku.dk.
11
Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark. Electronic address: lbpedersen@bio.ku.dk.

Abstract

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.

KEYWORDS:

BMP; CEP128; TGF-β; basal body; bone morphogenetic protein; centriole; centrosome; phosphoproteomics; primary cilium; subdistal appendage; transforming growth factor β; zebrafish

PMID:
29514088
DOI:
10.1016/j.celrep.2018.02.043
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