Centrosomal Protein DZIP1 Regulates Hedgehog Signaling by Promoting Cytoplasmic Retention of Transcription Factor GLI3 and Affecting Ciliogenesis

Wang, Chengbing; Low, Wee-Chuang; Liu, Aimin; Wang, Baolin

doi:10.1074/jbc.m113.492066

Cited by 44 publications

(62 citation statements)

References 48 publications

(46 reference statements)

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“…Interestingly, cilium-related proteins such as tubulin family members and DZIP1/Iguana were specifically purified with TAP-Cby1. DZIP1 has been shown to localize to mother centrioles and to play an essential role in primary cilium formation (38)(39)(40). It also binds to the Gli3 transcription factor to regulate Hedgehog signaling (38)(39)(40).…”

Section: Identification Of Fam92a As a Cby1-interacting Proteinmentioning

confidence: 99%

“…DZIP1 has been shown to localize to mother centrioles and to play an essential role in primary cilium formation (38)(39)(40). It also binds to the Gli3 transcription factor to regulate Hedgehog signaling (38)(39)(40). Further inspection of the list led us to focus on FAM92A for the following reasons: (i) its role in ciliogenesis is unknown; (ii) it contains a putative lipid-binding BAR domain, which is consistent with the localization and functional association of Cby1 with membranes (6); and (iii) it colocalizes with Cby1 at mother centrioles (see Fig.…”

Section: Identification Of Fam92a As a Cby1-interacting Proteinmentioning

confidence: 99%

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BAR Domain-Containing FAM92 Proteins Interact with Chibby1 To Facilitate Ciliogenesis

Chen

Fisher

et al. 2016

Molecular and Cellular Biology

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dChibby1 (Cby1) is a small, conserved coiled-coil protein that localizes to centrioles/basal bodies and plays a crucial role in the formation and function of cilia. During early stages of ciliogenesis, Cby1 is required for the efficient recruitment of small vesicles at the distal end of centrioles to facilitate basal body docking to the plasma membrane. Here, we identified family with sequence similarity 92, member A (FAM92A) and FAM92B, which harbor predicted lipid-binding BAR domains, as novel Cby1-interacting partners using tandem affinity purification and mass spectrometry. We found that in cultured cell lines, FAM92A colocalizes with Cby1 at the centrioles/basal bodies of primary cilia, while FAM92B is undetectable. In airway multiciliated cells, both FAM92A and -92B colocalize with Cby1 at the base of cilia. Notably, the centriolar localization of FAM92A and -92B depends largely on Cby1. Knockdown of FAM92A in RPE1 cells impairs ciliogenesis. Consistent with the membrane-remodeling properties of BAR domains, FAM92A and -92B in cooperation with Cby1 induce deformed membrane-like structures containing the small GTPase Rab8 in cultured cells. Our results therefore suggest that FAM92 proteins interact with Cby1 to promote ciliogenesis via regulation of membrane-remodeling processes.

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Section: Identification Of Fam92a As a Cby1-interacting Proteinmentioning

confidence: 99%

Section: Identification Of Fam92a As a Cby1-interacting Proteinmentioning

confidence: 99%

BAR Domain-Containing FAM92 Proteins Interact with Chibby1 To Facilitate Ciliogenesis

Chen

Fisher

et al. 2016

Molecular and Cellular Biology

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“…Fish with a Dzip1/iguana mutation develop an abnormal midline and body shape (9,10) with defects in the Hedgehog (Hh) signaling pathway (8,11). Dzip1 is also involved in Hh signaling in mice (12) by regulating the turnover of Gli proteins (12)(13)(14). In addition to its role in the regulation of Hh signaling, Dzip1 is also required for ciliogenesis in zebrafish Kupffer's vesicle cells (15,16) and in cultured mammalian cells (12,17,18).…”

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confidence: 99%

DAZ-interacting Protein 1 (Dzip1) Phosphorylation by Polo-like Kinase 1 (Plk1) Regulates the Centriolar Satellite Localization of the BBSome Protein during the Cell Cycle

Zhang

Wang

et al. 2017

Journal of Biological Chemistry

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“…Previous studies in cultured human cells suggested a redundant role for DZIP1 and DZIP1L in ciliogenesis 17 , a conclusion supported by our zebrafish in vivo experiments (data not shown). DZIP1 localizes to the basal body, the transition zone, and mother centriole 22,43 . Our findings reveal a similar localization pattern for DZIP1L, and proteomic studies in Chlamydomonas reinhardtii further support DZIP1L as a transition zone protein 44 .…”

Section: Discussionmentioning

confidence: 99%

“…2), and previous overexpression studies showed localization to the ciliary base 17 . In zebrafish and mice, we and others have implicated the paralogue Dzip1 in hedgehog (HH) signalling and ciliogenesis [18][19][20][21][22] , but there is little known about Dzip1l function in any organism.…”

Section: Dzip1l Is a New Arpkd Genementioning

confidence: 99%

Mutations in DZIP1L, which encodes a ciliary transition zone protein, cause autosomal recessive polycystic kidney disease

2017

Mechanisms of Development

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Author contributions LH, PJK, SYT, SV, and SR performed the zebrafish mutant and morphant analysis, protein interaction studies, localization experiments with human fibroblasts and validation of PC antibodies. WH supervised the protein interaction studies. EO, CK and DE performed the zebrafish morpholino analysis. MCRG, GK, VM and ADC performed the mouse analyses, and MCRG and GK performed the localization experiments with mouse cells. RT, PP and ACP performed the screen that identified the mouse mutant, and BW was involved in mapping and identifying the mouse mutation. GDW performed the superresolution microscopy experiments. MHL assisted with design and analysis of mouse kidney experiments. NOB, NH, VF, and SN performed the human mutation analysis. SN, VF, MH, HYG, EAO, FH, and CB carried out the WES data processing and analyses. SN, VF, EW, UV, HYG, KZ, FH, and CB recruited and clinically characterized the study subjects and collected samples. BH performed histologic evaluation of the data. SR, CW, and CB conceived the project, designed and supervised the experiments, analysed and interpreted the data, and wrote the manuscript. All authors reviewed the final manuscript. Competing financial interest statementThe authors declare that there are no competing financial interests. HHS Public AccessAuthor manuscript Nat Genet. Author manuscript; available in PMC 2018 January 01. AbstractAutosomal recessive polycystic kidney disease (ARPKD), usually considered to be a genetically homogeneous disease caused by mutations in PKHD1, has been associated with ciliary dysfunction. Here, we describe mutations in the DAZ interacting protein 1-like (DZIP1L) gene in patients with ARPKD, findings we have further validated by loss-of-function studies in mice and zebrafish. DZIP1L localizes to centrioles and at the distal end of basal bodies, and interacts with septin2, a protein implicated in maintenance of the periciliary diffusion barrier at the ciliary transition zone. Consistent with a defect in the diffusion barrier, we found that the ciliary membrane translocation of the PKD proteins, polycystin-1 and −2, is compromised in DZIP1L mutant cells. Together, these data provide the first conclusive evidence that ARPKD is not a homogeneous disorder, and establishes DZIP1L as a second gene involved in its pathogenesis.

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Centrosomal Protein DZIP1 Regulates Hedgehog Signaling by Promoting Cytoplasmic Retention of Transcription Factor GLI3 and Affecting Ciliogenesis

Cited by 44 publications

References 48 publications

BAR Domain-Containing FAM92 Proteins Interact with Chibby1 To Facilitate Ciliogenesis

BAR Domain-Containing FAM92 Proteins Interact with Chibby1 To Facilitate Ciliogenesis

DAZ-interacting Protein 1 (Dzip1) Phosphorylation by Polo-like Kinase 1 (Plk1) Regulates the Centriolar Satellite Localization of the BBSome Protein during the Cell Cycle

Mutations in DZIP1L, which encodes a ciliary transition zone protein, cause autosomal recessive polycystic kidney disease

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