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

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

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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. 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.

Original languageEnglish
JournalCell Reports
Volume22
Issue number10
Pages (from-to)2584-2592
ISSN2211-1247
DOIs
Publication statusPublished - 6. Mar 2018

Fingerprint

Centrioles
Bone Morphogenetic Proteins
Cilia
Transforming Growth Factors
Cells
Zebrafish
Phosphorylation
Animals
Proteins
Cultured Cells

Keywords

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

Cite this

Mönnich, Maren ; Borgeskov, Louise ; Breslin, Loretta ; Jakobsen, Lis ; Rogowski, Michaela ; Doganli, Canan ; Schrøder, Jacob M ; Mogensen, Johanne B ; Blinkenkjær, Louise ; Harder, Lea M ; Lundberg, Emma ; Geimer, Stefan ; Christensen, Søren T ; Andersen, Jens S ; Larsen, Lars A ; Pedersen, Lotte B. / CEP128 Localizes to the Subdistal Appendages of the Mother Centriole and Regulates TGF-β/BMP Signaling at the Primary Cilium. In: Cell Reports. 2018 ; Vol. 22, No. 10. pp. 2584-2592.
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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. M{\"o}nnich 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.",
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author = "Maren M{\"o}nnich and Louise Borgeskov and Loretta Breslin and Lis Jakobsen and Michaela Rogowski and Canan Doganli and Schr{\o}der, {Jacob M} and Mogensen, {Johanne B} and Louise Blinkenkj{\ae}r and Harder, {Lea M} and Emma Lundberg and Stefan Geimer and Christensen, {S{\o}ren T} and Andersen, {Jens S} and Larsen, {Lars A} and Pedersen, {Lotte B}",
note = "Copyright {\circledC} 2018 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2018",
month = "3",
day = "6",
doi = "10.1016/j.celrep.2018.02.043",
language = "English",
volume = "22",
pages = "2584--2592",
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Mönnich, M, Borgeskov, L, Breslin, L, Jakobsen, L, Rogowski, M, Doganli, C, Schrøder, JM, Mogensen, JB, Blinkenkjær, L, Harder, LM, Lundberg, E, Geimer, S, Christensen, ST, Andersen, JS, Larsen, LA & Pedersen, LB 2018, 'CEP128 Localizes to the Subdistal Appendages of the Mother Centriole and Regulates TGF-β/BMP Signaling at the Primary Cilium', Cell Reports, vol. 22, no. 10, pp. 2584-2592. https://doi.org/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. / Mönnich, Maren; Borgeskov, Louise; Breslin, Loretta; Jakobsen, Lis; Rogowski, Michaela; Doganli, Canan; Schrøder, Jacob M; Mogensen, Johanne B; Blinkenkjær, Louise; Harder, Lea M; Lundberg, Emma; Geimer, Stefan; Christensen, Søren T; Andersen, Jens S; Larsen, Lars A; Pedersen, Lotte B.

In: Cell Reports, Vol. 22, No. 10, 06.03.2018, p. 2584-2592.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - CEP128 Localizes to the Subdistal Appendages of the Mother Centriole and Regulates TGF-β/BMP Signaling at the Primary Cilium

AU - Mönnich, Maren

AU - Borgeskov, Louise

AU - Breslin, Loretta

AU - Jakobsen, Lis

AU - Rogowski, Michaela

AU - Doganli, Canan

AU - Schrøder, Jacob M

AU - Mogensen, Johanne B

AU - Blinkenkjær, Louise

AU - Harder, Lea M

AU - Lundberg, Emma

AU - Geimer, Stefan

AU - Christensen, Søren T

AU - Andersen, Jens S

AU - Larsen, Lars A

AU - Pedersen, Lotte B

N1 - Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2018/3/6

Y1 - 2018/3/6

N2 - 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.

AB - 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.

KW - BMP

KW - CEP128

KW - TGF-β

KW - basal body

KW - bone morphogenetic protein

KW - centriole

KW - centrosome

KW - phosphoproteomics

KW - primary cilium

KW - subdistal appendage

KW - transforming growth factor β

KW - zebrafish

U2 - 10.1016/j.celrep.2018.02.043

DO - 10.1016/j.celrep.2018.02.043

M3 - Journal article

C2 - 29514088

VL - 22

SP - 2584

EP - 2592

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 10

ER -