CEP128 Localizes to the Subdistal Appendages of the Mother Centriole and Regulates TGF-β/BMP Signaling at the Primary Cilium
Summary: 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...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-03-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718302249 |
| id |
doaj-a68234e28fda4bce9920a039ecebb8ef |
|---|---|
| record_format |
Article |
| spelling |
doaj-a68234e28fda4bce9920a039ecebb8ef2020-11-25T01:31:30ZengElsevierCell Reports2211-12472018-03-01221025842592CEP128 Localizes to the Subdistal Appendages of the Mother Centriole and Regulates TGF-β/BMP Signaling at the Primary CiliumMaren Mönnich0Louise Borgeskov1Loretta Breslin2Lis Jakobsen3Michaela Rogowski4Canan Doganli5Jacob M. Schrøder6Johanne B. Mogensen7Louise Blinkenkjær8Lea M. Harder9Emma Lundberg10Stefan Geimer11Søren T. Christensen12Jens S. Andersen13Lars A. Larsen14Lotte B. Pedersen15Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, DenmarkDepartment of Biology, University of Copenhagen, DK-2100 Copenhagen, DenmarkDepartment 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, DenmarkDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, DenmarkCell Biology/Electron Microscopy, University of Bayreuth, Universitaetsstrasse 30, 95440 Bayreuth, GermanyDepartment of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, DenmarkDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, DenmarkDepartment of Biology, University of Copenhagen, DK-2100 Copenhagen, DenmarkDepartment of Biology, University of Copenhagen, DK-2100 Copenhagen, DenmarkDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, DenmarkScience for Life Laboratory, School of Biotechnology, KTH Royal Institute of Technology, SE-171 21 Stockholm, SwedenCell Biology/Electron Microscopy, University of Bayreuth, Universitaetsstrasse 30, 95440 Bayreuth, Germany; Corresponding authorDepartment of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark; Corresponding authorDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark; Corresponding authorDepartment of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark; Corresponding authorDepartment of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark; Corresponding authorSummary: 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. Keywords: primary cilium, basal body, centriole, subdistal appendage, centrosome, transforming growth factor β, TGF-β, bone morphogenetic protein, BMP, zebrafish, phosphoproteomics, CEP128http://www.sciencedirect.com/science/article/pii/S2211124718302249 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Maren Mönnich Louise Borgeskov Loretta Breslin Lis Jakobsen Michaela Rogowski Canan Doganli Jacob M. Schrøder Johanne B. Mogensen Louise Blinkenkjær Lea M. Harder Emma Lundberg Stefan Geimer Søren T. Christensen Jens S. Andersen Lars A. Larsen Lotte B. Pedersen |
| spellingShingle |
Maren Mönnich Louise Borgeskov Loretta Breslin Lis Jakobsen Michaela Rogowski Canan Doganli Jacob M. Schrøder Johanne B. Mogensen Louise Blinkenkjær Lea M. Harder Emma Lundberg Stefan Geimer Søren T. Christensen Jens S. Andersen Lars A. Larsen Lotte B. Pedersen CEP128 Localizes to the Subdistal Appendages of the Mother Centriole and Regulates TGF-β/BMP Signaling at the Primary Cilium Cell Reports |
| author_facet |
Maren Mönnich Louise Borgeskov Loretta Breslin Lis Jakobsen Michaela Rogowski Canan Doganli Jacob M. Schrøder Johanne B. Mogensen Louise Blinkenkjær Lea M. Harder Emma Lundberg Stefan Geimer Søren T. Christensen Jens S. Andersen Lars A. Larsen Lotte B. Pedersen |
| author_sort |
Maren Mönnich |
| title |
CEP128 Localizes to the Subdistal Appendages of the Mother Centriole and Regulates TGF-β/BMP Signaling at the Primary Cilium |
| title_short |
CEP128 Localizes to the Subdistal Appendages of the Mother Centriole and Regulates TGF-β/BMP Signaling at the Primary Cilium |
| title_full |
CEP128 Localizes to the Subdistal Appendages of the Mother Centriole and Regulates TGF-β/BMP Signaling at the Primary Cilium |
| title_fullStr |
CEP128 Localizes to the Subdistal Appendages of the Mother Centriole and Regulates TGF-β/BMP Signaling at the Primary Cilium |
| title_full_unstemmed |
CEP128 Localizes to the Subdistal Appendages of the Mother Centriole and Regulates TGF-β/BMP Signaling at the Primary Cilium |
| title_sort |
cep128 localizes to the subdistal appendages of the mother centriole and regulates tgf-β/bmp signaling at the primary cilium |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2018-03-01 |
| description |
Summary: 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. Keywords: primary cilium, basal body, centriole, subdistal appendage, centrosome, transforming growth factor β, TGF-β, bone morphogenetic protein, BMP, zebrafish, phosphoproteomics, CEP128 |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124718302249 |
| work_keys_str_mv |
AT marenmonnich cep128localizestothesubdistalappendagesofthemothercentrioleandregulatestgfbbmpsignalingattheprimarycilium AT louiseborgeskov cep128localizestothesubdistalappendagesofthemothercentrioleandregulatestgfbbmpsignalingattheprimarycilium AT lorettabreslin cep128localizestothesubdistalappendagesofthemothercentrioleandregulatestgfbbmpsignalingattheprimarycilium AT lisjakobsen cep128localizestothesubdistalappendagesofthemothercentrioleandregulatestgfbbmpsignalingattheprimarycilium AT michaelarogowski cep128localizestothesubdistalappendagesofthemothercentrioleandregulatestgfbbmpsignalingattheprimarycilium AT canandoganli cep128localizestothesubdistalappendagesofthemothercentrioleandregulatestgfbbmpsignalingattheprimarycilium AT jacobmschrøder cep128localizestothesubdistalappendagesofthemothercentrioleandregulatestgfbbmpsignalingattheprimarycilium AT johannebmogensen cep128localizestothesubdistalappendagesofthemothercentrioleandregulatestgfbbmpsignalingattheprimarycilium AT louiseblinkenkjær cep128localizestothesubdistalappendagesofthemothercentrioleandregulatestgfbbmpsignalingattheprimarycilium AT leamharder cep128localizestothesubdistalappendagesofthemothercentrioleandregulatestgfbbmpsignalingattheprimarycilium AT emmalundberg cep128localizestothesubdistalappendagesofthemothercentrioleandregulatestgfbbmpsignalingattheprimarycilium AT stefangeimer cep128localizestothesubdistalappendagesofthemothercentrioleandregulatestgfbbmpsignalingattheprimarycilium AT sørentchristensen cep128localizestothesubdistalappendagesofthemothercentrioleandregulatestgfbbmpsignalingattheprimarycilium AT jenssandersen cep128localizestothesubdistalappendagesofthemothercentrioleandregulatestgfbbmpsignalingattheprimarycilium AT larsalarsen cep128localizestothesubdistalappendagesofthemothercentrioleandregulatestgfbbmpsignalingattheprimarycilium AT lottebpedersen cep128localizestothesubdistalappendagesofthemothercentrioleandregulatestgfbbmpsignalingattheprimarycilium |
| _version_ |
1725086339240558592 |