scholarly journals Trichoplein keeps primary cilia silent

2012 ◽  
Vol 197 (3) ◽  
pp. 341-341 ◽  
Author(s):  
Ben Short
Keyword(s):  
Primary Cilia ◽  
Aurora A ◽  
Proliferating Cells

Study identifies a centriolar protein that activates Aurora A to suppress ciliogenesis in proliferating cells.

scholarly journals Ndel1 suppresses ciliogenesis in proliferating cells by regulating the trichoplein–Aurora A pathway

2016 ◽  
Vol 212 (4) ◽  
pp. 409-423 ◽  
Author(s):  
Hironori Inaba ◽  
Hidemasa Goto ◽  
Kousuke Kasahara ◽  
Kanako Kumamoto ◽  
Shigenobu Yonemura ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Serum Starvation ◽  
Aurora A ◽  
Proliferating Cells ◽  
Quiescent Cells ◽  
Cell Cycle Reentry ◽  
Upstream Regulator ◽  
Cilia Formation ◽  
Mother Centriole ◽  
Component Protein

Primary cilia protrude from the surface of quiescent cells and disassemble at cell cycle reentry. We previously showed that ciliary reassembly is suppressed by trichoplein-mediated Aurora A activation pathway in growing cells. Here, we report that Ndel1, a well-known modulator of dynein activity, localizes at the subdistal appendage of the mother centriole, which nucleates a primary cilium. In the presence of serum, Ndel1 depletion reduces trichoplein at the mother centriole and induces unscheduled primary cilia formation, which is reverted by forced trichoplein expression or coknockdown of KCTD17 (an E3 ligase component protein for trichoplein). Serum starvation induced transient Ndel1 degradation, subsequent to the disappearance of trichoplein at the mother centriole. Forced expression of Ndel1 suppressed trichoplein degradation and axonemal microtubule extension during ciliogenesis, similar to trichoplein induction or KCTD17 knockdown. Most importantly, the proportion of ciliated and quiescent cells was increased in the kidney tubular epithelia of newborn Ndel1-hypomorphic mice. Thus, Ndel1 acts as a novel upstream regulator of the trichoplein–Aurora A pathway to inhibit primary cilia assembly.

scholarly journals Trichoplein and Aurora A block aberrant primary cilia assembly in proliferating cells

2012 ◽  
Vol 197 (3) ◽  
pp. 391-405 ◽  
Author(s):  
Akihito Inoko ◽  
Makoto Matsuyama ◽  
Hidemasa Goto ◽  
Yuki Ohmuro-Matsuyama ◽  
Yuko Hayashi ◽  
...  
Keyword(s):  
Primary Cilia ◽  
G1 Arrest ◽  
Aurora A ◽  
Proliferating Cells ◽  
Quiescent Cells ◽  
Cilia Formation ◽  
Mother And Daughter ◽  
Exogenous Expression ◽  
Sensory Functions

The primary cilium is an antenna-like organelle that modulates differentiation, sensory functions, and signal transduction. After cilia are disassembled at the G0/G1 transition, formation of cilia is strictly inhibited in proliferating cells. However, the mechanisms of this inhibition are unknown. In this paper, we show that trichoplein disappeared from the basal body in quiescent cells, whereas it localized to mother and daughter centrioles in proliferating cells. Exogenous expression of trichoplein inhibited primary cilia assembly in serum-starved cells, whereas ribonucleic acid interference–mediated depletion induced primary cilia assembly upon cultivation with serum. Trichoplein controlled Aurora A (AurA) activation at the centrioles predominantly in G1 phase. In vitro analyses confirmed that trichoplein bound and activated AurA directly. Using trichoplein mutants, we demonstrate that the suppression of primary cilia assembly by trichoplein required its ability not only to localize to centrioles but also to bind and activate AurA. Trichoplein or AurA knockdown also induced G0/G1 arrest, but this phenotype was reversed when cilia formation was prevented by simultaneous knockdown of IFT-20. These data suggest that the trichoplein–AurA pathway is required for G1 progression through a key role in the continuous suppression of primary cilia assembly.

scholarly journals Over-expression of Plk4 induces centrosome amplification, loss of primary cilia and associated tissue hyperplasia in the mouse

Open Biology ◽  
2015 ◽  
Vol 5 (12) ◽  
pp. 150209 ◽  
Author(s):  
Paula A. Coelho ◽  
Leah Bury ◽  
Marta N. Shahbazi ◽  
Kifayathullah Liakath-Ali ◽  
Peri H. Tate ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Primary Cultures ◽  
Centrosome Amplification ◽  
Proliferating Cells ◽  
Differentiation Markers ◽  
Over Expression ◽  
Centriole Duplication ◽  
Keratin 5 ◽  
Tumour Formation ◽  
Tumour Suppressor P53

To address the long-known relationship between supernumerary centrosomes and cancer, we have generated a transgenic mouse that permits inducible expression of the master regulator of centriole duplication, Polo-like-kinase-4 (Plk4). Over-expression of Plk4 from this transgene advances the onset of tumour formation that occurs in the absence of the tumour suppressor p53. Plk4 over-expression also leads to hyperproliferation of cells in the pancreas and skin that is enhanced in a p53 null background. Pancreatic islets become enlarged following Plk4 over-expression as a result of equal expansion of α- and β-cells, which exhibit centrosome amplification. Mice overexpressing Plk4 develop grey hair due to a loss of differentiated melanocytes and bald patches of skin associated with a thickening of the epidermis. This reflects an increase in proliferating cells expressing keratin 5 in the basal epidermal layer and the expansion of these cells into suprabasal layers. Such cells also express keratin 6, a marker for hyperplasia. This is paralleled by a decreased expression of later differentiation markers, involucrin, filaggrin and loricrin. Proliferating cells showed an increase in centrosome number and a loss of primary cilia, events that were mirrored in primary cultures of keratinocytes established from these animals. We discuss how repeated duplication of centrioles appears to prevent the formation of basal bodies leading to loss of primary cilia, disruption of signalling and thereby aberrant differentiation of cells within the epidermis. The absence of p53 permits cells with increased centrosomes to continue dividing, thus setting up a neoplastic state of error prone mitoses, a prerequisite for cancer development.

scholarly journals KIF14 controls ciliogenesis via regulation of Aurora A and is important for Hedgehog signaling

2020 ◽  
Vol 219 (6) ◽  
Author(s):  
Petra Pejskova ◽  
Madeline Louise Reilly ◽  
Lucia Bino ◽  
Ondrej Bernatik ◽  
Linda Dolanska ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Primary Cilium ◽  
Hedgehog Signaling ◽  
Cell Cycle Progression ◽  
Primary Cilia ◽  
Aurora A ◽  
Pathway Activation ◽  
Cilia Formation ◽  
Tightly Coupled ◽  
Hh Signaling

Primary cilia play critical roles in development and disease. Their assembly and disassembly are tightly coupled to cell cycle progression. Here, we present data identifying KIF14 as a regulator of cilia formation and Hedgehog (HH) signaling. We show that RNAi depletion of KIF14 specifically leads to defects in ciliogenesis and basal body (BB) biogenesis, as its absence hampers the efficiency of primary cilium formation and the dynamics of primary cilium elongation, and disrupts the localization of the distal appendage proteins SCLT1 and FBF1 and components of the IFT-B complex. We identify deregulated Aurora A activity as a mechanism contributing to the primary cilium and BB formation defects seen after KIF14 depletion. In addition, we show that primary cilia in KIF14-depleted cells are defective in response to HH pathway activation, independently of the effects of Aurora A. In sum, our data point to KIF14 as a critical node connecting cell cycle machinery, effective ciliogenesis, and HH signaling.

scholarly journals CEP55 promotes cilia disassembly through stabilizing Aurora A kinase

2021 ◽  
Vol 220 (2) ◽  
Author(s):  
Yu-Cheng Zhang ◽  
Yun-Feng Bai ◽  
Jin-Feng Yuan ◽  
Xiao-Lin Shen ◽  
Yu-Ling Xu ◽  
...  
Keyword(s):  
Cell Surface ◽  
Primary Cilia ◽  
Perinatal Death ◽  
Clinical Manifestations ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Mammalian Development ◽  
Polycystic Kidneys ◽  
And Control

Primary cilia protrude from the cell surface and have diverse roles during development and disease, which depends on the precise timing and control of cilia assembly and disassembly. Inactivation of assembly often causes cilia defects and underlies ciliopathy, while diseases caused by dysfunction in disassembly remain largely unknown. Here, we demonstrate that CEP55 functions as a cilia disassembly regulator to participate in ciliopathy. Cep55−/− mice display clinical manifestations of Meckel–Gruber syndrome, including perinatal death, polycystic kidneys, and abnormalities in the CNS. Interestingly, Cep55−/− mice exhibit an abnormal elongation of cilia on these tissues. Mechanistically, CEP55 promotes cilia disassembly by interacting with and stabilizing Aurora A kinase, which is achieved through facilitating the chaperonin CCT complex to Aurora A. In addition, CEP55 mutation in Meckel–Gruber syndrome causes the failure of cilia disassembly. Thus, our study establishes a cilia disassembly role for CEP55 in vivo, coupling defects in cilia disassembly to ciliopathy and further suggesting that proper cilia dynamics are critical for mammalian development.

scholarly journals Prdx1 Promotes the Loss of Primary Cilia in Esophageal Squamous Cell Carcinoma

2019 ◽  
Author(s):  
Fanghua Gong ◽  
Qiongzhen Chen ◽  
Jinmeng Li ◽  
Xiaoning Yang ◽  
Junfeng Ma ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Primary Cilia ◽  
Molecular Mechanisms ◽  
Tumor Formation ◽  
Aurora A ◽  
Cilia Formation ◽  
Signaling Axis

Abstract Background: Loss of primary cilia is frequently observed in tumor cells, suggesting that the absence of this organelle may promote tumorigenesis through aberrant signal transduction, the inability to exit the cell cycle, and promotion of tumor cell invasion. Primary cilia loss also occurs in esophageal squamous cell carcinoma (ESCC) cells, but the molecular mechanisms that explain how ESCC cells lose primary cilia remain poorly understood. Methods: Inhibiting the expression of Prdx1 in the ESCC cells to detect the up-regulated genes related to cilium regeneration and down-regulated genes related to cilium disassembly by Gene chip. And, mice and cell experiments were carried to confirm the role of the HEF1-Aurora A-HDAC6 signaling axis in ESCC. Results: In this study, we found that silencing Peroxiredoxin 1 (Prdx1) restores primary cilia formation, and over-expressing Prdx1 induces primary cilia loss in ESCC cells. We also showed that the expression of Prdx1 regulates the action of the HEF1-Aurora A-HDAC6 signaling axis to promote the disassembly of primary cilia, and suppression of Prdx1 results in decreased tumor formation and tumor mass volume in vivo. Conclusions: These results suggest that Prdx1 is a novel regulator of primary cilia formation in ESCC cells.

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