Arl13b and the exocyst interact synergistically in ciliogenesis

Cecilia Seixas, Soo Young Choi, Noemi Polgar, Nicole L. Umberger, Michael P. East, Xiaofeng Zuo, Hugo Moreiras, Rania Ghossoub, Alexandre Benmerah, Richard A. Kahn, Ben Fogelgren, Tamara Caspary, Joshua H. Lipschutz, Duarte C. Barral

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Arl13b belongs to the ADP-ribosylation factor family within the Ras superfamily of regulatory GTPases. Mutations in Arl13b cause Joubert syndrome, which is characterized by congenital cerebellar ataxia, hypotonia, oculomotor apraxia, and mental retardation. Arl13b is highly enriched in cilia and is required for ciliogenesis in multiple organs. Nevertheless, the precise role of Arl13b remains elusive. Here we report that the exocyst subunits Sec8, Exo70, and Sec5 bind preferentially to the GTP-bound form of Arl13b, consistent with the exocyst being an effector of Arl13b. Moreover, we show that Arl13b binds directly to Sec8 and Sec5. In zebrafish, depletion of arl13b or the exocyst subunit sec10 causes phenotypes characteristic of defective cilia, such as curly tail up, edema, and abnormal pronephric kidney development. We explored this further and found a synergistic genetic interaction between arl13b and sec10 morphants in cilia-dependent phenotypes. Through conditional deletion of Arl13b or Sec10 in mice, we found kidney cysts and decreased ciliogenesis in cells surrounding the cysts. Moreover, we observed a decrease in Arl13b expression in the kidneys from Sec10 conditional knockout mice. Taken together, our results indicate that Arl13b and the exocyst function together in the same pathway leading to functional cilia.

Original languageEnglish
Pages (from-to)308-320
Number of pages13
JournalMolecular Biology of the Cell
Volume27
Issue number2
DOIs
Publication statusPublished - 15 Jan 2016

Fingerprint

Cilia
Kidney
Cysts
ADP-Ribosylation Factors
Phenotype
Apraxias
Cerebellar Ataxia
Muscle Hypotonia
GTP Phosphohydrolases
Zebrafish
Guanosine Triphosphate
Knockout Mice
Intellectual Disability
Tail
Edema
Mutation

Cite this

Seixas, Cecilia ; Choi, Soo Young ; Polgar, Noemi ; Umberger, Nicole L. ; East, Michael P. ; Zuo, Xiaofeng ; Moreiras, Hugo ; Ghossoub, Rania ; Benmerah, Alexandre ; Kahn, Richard A. ; Fogelgren, Ben ; Caspary, Tamara ; Lipschutz, Joshua H. ; Barral, Duarte C. / Arl13b and the exocyst interact synergistically in ciliogenesis. In: Molecular Biology of the Cell. 2016 ; Vol. 27, No. 2. pp. 308-320.
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abstract = "Arl13b belongs to the ADP-ribosylation factor family within the Ras superfamily of regulatory GTPases. Mutations in Arl13b cause Joubert syndrome, which is characterized by congenital cerebellar ataxia, hypotonia, oculomotor apraxia, and mental retardation. Arl13b is highly enriched in cilia and is required for ciliogenesis in multiple organs. Nevertheless, the precise role of Arl13b remains elusive. Here we report that the exocyst subunits Sec8, Exo70, and Sec5 bind preferentially to the GTP-bound form of Arl13b, consistent with the exocyst being an effector of Arl13b. Moreover, we show that Arl13b binds directly to Sec8 and Sec5. In zebrafish, depletion of arl13b or the exocyst subunit sec10 causes phenotypes characteristic of defective cilia, such as curly tail up, edema, and abnormal pronephric kidney development. We explored this further and found a synergistic genetic interaction between arl13b and sec10 morphants in cilia-dependent phenotypes. Through conditional deletion of Arl13b or Sec10 in mice, we found kidney cysts and decreased ciliogenesis in cells surrounding the cysts. Moreover, we observed a decrease in Arl13b expression in the kidneys from Sec10 conditional knockout mice. Taken together, our results indicate that Arl13b and the exocyst function together in the same pathway leading to functional cilia.",
author = "Cecilia Seixas and Choi, {Soo Young} and Noemi Polgar and Umberger, {Nicole L.} and East, {Michael P.} and Xiaofeng Zuo and Hugo Moreiras and Rania Ghossoub and Alexandre Benmerah and Kahn, {Richard A.} and Ben Fogelgren and Tamara Caspary and Lipschutz, {Joshua H.} and Barral, {Duarte C.}",
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Seixas, C, Choi, SY, Polgar, N, Umberger, NL, East, MP, Zuo, X, Moreiras, H, Ghossoub, R, Benmerah, A, Kahn, RA, Fogelgren, B, Caspary, T, Lipschutz, JH & Barral, DC 2016, 'Arl13b and the exocyst interact synergistically in ciliogenesis', Molecular Biology of the Cell, vol. 27, no. 2, pp. 308-320. https://doi.org/10.1091/mbc.E15-02-0061

Arl13b and the exocyst interact synergistically in ciliogenesis. / Seixas, Cecilia; Choi, Soo Young; Polgar, Noemi; Umberger, Nicole L.; East, Michael P.; Zuo, Xiaofeng; Moreiras, Hugo; Ghossoub, Rania; Benmerah, Alexandre; Kahn, Richard A.; Fogelgren, Ben; Caspary, Tamara; Lipschutz, Joshua H.; Barral, Duarte C.

In: Molecular Biology of the Cell, Vol. 27, No. 2, 15.01.2016, p. 308-320.

Research output: Contribution to journalArticle

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T1 - Arl13b and the exocyst interact synergistically in ciliogenesis

AU - Seixas, Cecilia

AU - Choi, Soo Young

AU - Polgar, Noemi

AU - Umberger, Nicole L.

AU - East, Michael P.

AU - Zuo, Xiaofeng

AU - Moreiras, Hugo

AU - Ghossoub, Rania

AU - Benmerah, Alexandre

AU - Kahn, Richard A.

AU - Fogelgren, Ben

AU - Caspary, Tamara

AU - Lipschutz, Joshua H.

AU - Barral, Duarte C.

PY - 2016/1/15

Y1 - 2016/1/15

N2 - Arl13b belongs to the ADP-ribosylation factor family within the Ras superfamily of regulatory GTPases. Mutations in Arl13b cause Joubert syndrome, which is characterized by congenital cerebellar ataxia, hypotonia, oculomotor apraxia, and mental retardation. Arl13b is highly enriched in cilia and is required for ciliogenesis in multiple organs. Nevertheless, the precise role of Arl13b remains elusive. Here we report that the exocyst subunits Sec8, Exo70, and Sec5 bind preferentially to the GTP-bound form of Arl13b, consistent with the exocyst being an effector of Arl13b. Moreover, we show that Arl13b binds directly to Sec8 and Sec5. In zebrafish, depletion of arl13b or the exocyst subunit sec10 causes phenotypes characteristic of defective cilia, such as curly tail up, edema, and abnormal pronephric kidney development. We explored this further and found a synergistic genetic interaction between arl13b and sec10 morphants in cilia-dependent phenotypes. Through conditional deletion of Arl13b or Sec10 in mice, we found kidney cysts and decreased ciliogenesis in cells surrounding the cysts. Moreover, we observed a decrease in Arl13b expression in the kidneys from Sec10 conditional knockout mice. Taken together, our results indicate that Arl13b and the exocyst function together in the same pathway leading to functional cilia.

AB - Arl13b belongs to the ADP-ribosylation factor family within the Ras superfamily of regulatory GTPases. Mutations in Arl13b cause Joubert syndrome, which is characterized by congenital cerebellar ataxia, hypotonia, oculomotor apraxia, and mental retardation. Arl13b is highly enriched in cilia and is required for ciliogenesis in multiple organs. Nevertheless, the precise role of Arl13b remains elusive. Here we report that the exocyst subunits Sec8, Exo70, and Sec5 bind preferentially to the GTP-bound form of Arl13b, consistent with the exocyst being an effector of Arl13b. Moreover, we show that Arl13b binds directly to Sec8 and Sec5. In zebrafish, depletion of arl13b or the exocyst subunit sec10 causes phenotypes characteristic of defective cilia, such as curly tail up, edema, and abnormal pronephric kidney development. We explored this further and found a synergistic genetic interaction between arl13b and sec10 morphants in cilia-dependent phenotypes. Through conditional deletion of Arl13b or Sec10 in mice, we found kidney cysts and decreased ciliogenesis in cells surrounding the cysts. Moreover, we observed a decrease in Arl13b expression in the kidneys from Sec10 conditional knockout mice. Taken together, our results indicate that Arl13b and the exocyst function together in the same pathway leading to functional cilia.

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