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

Li, Feng-Qian; Chen, Xingwang; Fisher, Cody R.; Siller, Saul S.; Zelikman, Klara; Kuriyama, Ryoko; Takemaru, Ken‐Ichi

doi:10.1128/mcb.00160-16

Cited by 44 publications

(57 citation statements)

References 61 publications

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“…S9A, B). GFP-Chibby1 and tdTomato-FAM92A form clusters within the cell cytoplasm as previously shown (37) and the analysis of line scan showed strong colocalization between constructs, suggesting an interaction between both tagged proteins (Supplemental Fig. S9A).…”

Section: Resultssupporting

confidence: 84%

“…(37) Cos-7 cells were cotransfected with GFP-Chibby1 and tdTomato-FAM92A or tdTomato-FAM92A R160* constructs (Supplemental Fig. S9A, B).…”

Section: Resultsmentioning

confidence: 99%

“…When FAM92A is knocked down in cells, an impaired ciliogenesis is observed. (37,39) FAM92A localization was detected at the transition zone of the primary cilium in IMCD3 cells. (39) In addition, FAM92A interacts with Cby1 (Chibby1) at the ciliary base to promote ciliogenesis via regulation of membrane-remodeling processes.…”

Section: Discussionmentioning

confidence: 98%

“…(37) Cby1 knockout mice show several hallmarks of ciliary defects, including chronic upper airway infection, subfertility, and polycystic kidneys as well as polydactyly and hydrocephalus at low frequencies. (37) …”

Section: Discussionmentioning

confidence: 99%

“…The p.Arg160 Ã truncated protein disrupts FAM92A homodimerization Because FAM92A can homodimerize, (37) we next investigated if the p.Arg160 Ã truncated protein could disrupt FAM92A/FAM92A interaction. Cos-7 cells were cotransfected with GFP-FAM92A and tdTomato-FAM92A or tdTomato-FAM92A R160 Ã constructs (Supplemental Fig.…”

Section: Linkage Analysis and Exome Sequencingmentioning

confidence: 99%

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FAM92A Underlies Nonsyndromic Postaxial Polydactyly in Humans and an Abnormal Limb and Digit Skeletal Phenotype in Mice

Schrauwen

Giese

Aziz

et al. 2018

Journal of Bone and Mineral Research

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Polydactyly is a common congenital anomaly of the hand and foot. Postaxial polydactyly (PAP) is characterized by one or more posterior or postaxial digits. In a Pakistani family with autosomal recessive nonsyndromic postaxial polydactyly type A (PAPA), we performed genomewide genotyping, linkage analysis, and exome and Sanger sequencing. Exome sequencing revealed a homozygous nonsense variant (c.478C>T, p.[Arg160*]) in the FAM92A gene within the mapped region on 8q21.13-q24.12 that segregated with the PAPA phenotype. We found that FAM92A is expressed in the developing mouse limb and E11.5 limb bud including the progress zone and the apical ectodermal ridge, where it strongly localizes at the cilia level, suggesting an important role in limb patterning. The identified variant leads to a loss of the FAM92A/Chibby1 complex that is crucial for ciliogenesis and impairs the recruitment and the colocalization of FAM92A with Chibby1 at the base of the cilia. In addition, we show that Fam92a−/− homozygous mice also exhibit an abnormal digit morphology, including metatarsal osteomas and polysyndactyly, in addition to distinct abnormalities on the deltoid tuberosity of their humeri. In conclusion, we present a new nonsyndromic PAPA ciliopathy due to a loss-of-function variant in FAM92A.

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Section: Resultssupporting

confidence: 84%

“…(37) Cos-7 cells were cotransfected with GFP-Chibby1 and tdTomato-FAM92A or tdTomato-FAM92A R160* constructs (Supplemental Fig. S9A, B).…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Linkage Analysis and Exome Sequencingmentioning

confidence: 99%

See 3 more Smart Citations

FAM92A Underlies Nonsyndromic Postaxial Polydactyly in Humans and an Abnormal Limb and Digit Skeletal Phenotype in Mice

Schrauwen

Giese

Aziz

et al. 2018

Journal of Bone and Mineral Research

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The ARPKD Protein DZIP1L Regulates Ciliary Protein Entry by Modulating the Architecture and Function of Ciliary Transition Fibers

Chen,

Wu,

Yan

et al. 2024

Advanced Science

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Serving as the cell's sensory antennae, primary cilia are linked to numerous human genetic diseases when they malfunction. DZIP1L, identified as one of the genetic causes of human autosomal recessive polycystic kidney disease (ARPKD), is an evolutionarily conserved ciliary basal body protein. Although it has been reported that DZIP1L is involved in the ciliary entry of PKD proteins, the underlying mechanism remains elusive. Here, an uncharacterized role of DZIP1L is reported in modulating the architecture and function of transition fibers (TFs), striking ciliary base structures essential for selective cilia gating. Using C. elegans as a model, C01G5.7 (hereafter termed DZIP‐1) is identified as the sole homolog of DZIP1L, which specifically localizes to TFs. While DZIP‐1 or ANKR‐26 (the ortholog of ANKRD26) deficiency shows subtle impact on TFs, co‐depletion of DZIP‐1 and ANKR‐26 disrupts TF assembly and cilia gating for soluble and membrane proteins, including the ortholog of ADPKD protein polycystin‐2. Notably, the synergistic role for DZIP1L and ANKRD26 in the formation and function of TFs is highly conserved in mammalian cilia. Hence, the findings illuminate an evolutionarily conserved role of DZIP1L in TFs architecture and function, highlighting TFs as a vital part of the ciliary gate implicated in ciliopathies ARPKD.

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DZIP1 regulates mammalian cardiac valve development through a Cby1‐β‐catenin mechanism

Guo

Beck

Fulmer

et al. 2021

Developmental Dynamics

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Background Mitral valve prolapse (MVP) is a common and progressive cardiovascular disease with developmental origins. How developmental errors contribute to disease pathogenesis are not well understood. Results A multimeric complex was identified that consists of the MVP gene Dzip1, Cby1, and β‐catenin. Co‐expression during valve development revealed overlap at the basal body of the primary cilia. Biochemical studies revealed a DZIP1 peptide required for stabilization of the complex and suppression of β‐catenin activities. Decoy peptides generated against this interaction motif altered nuclear vs cytosolic levels of β‐catenin with effects on transcriptional activity. A mutation within this domain was identified in a family with inherited non‐syndromic MVP. This novel mutation and our previously identified DZIP1S24R variant resulted in reduced DZIP1 and CBY1 stability and increased β‐catenin activities. The β‐catenin target gene, MMP2 was up‐regulated in the Dzip1S14R/+ valves and correlated with loss of collagenous ECM matrix and myxomatous phenotype. Conclusion Dzip1 functions to restrain β‐catenin signaling through a CBY1 linker during cardiac development. Loss of these interactions results in increased nuclear β‐catenin/Lef1 and excess MMP2 production, which correlates with developmental and postnatal changes in ECM and generation of a myxomatous phenotype.

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

Cited by 44 publications

References 61 publications

FAM92A Underlies Nonsyndromic Postaxial Polydactyly in Humans and an Abnormal Limb and Digit Skeletal Phenotype in Mice

FAM92A Underlies Nonsyndromic Postaxial Polydactyly in Humans and an Abnormal Limb and Digit Skeletal Phenotype in Mice

The ARPKD Protein DZIP1L Regulates Ciliary Protein Entry by Modulating the Architecture and Function of Ciliary Transition Fibers

DZIP1 regulates mammalian cardiac valve development through a Cby1‐β‐catenin mechanism

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