scholarly journals Role of Ocrl1 and Inpp5E in primary cilia assembly and maintenance: a phosphatidylinositol phosphatase relay system?

2016 ◽  
pp. 15
Author(s):  
R. Claudio Aguilar ◽  
Kayalvizhi Madhivanan ◽  
Swetha Ramadesika
Keyword(s):  
Primary Cilia ◽  
Relay System

scholarly journals Centrin2 regulates CP110 removal in primary cilium formation

2015 ◽  
Vol 208 (6) ◽  
pp. 693-701 ◽  
Author(s):  
Suzanna L. Prosser ◽  
Ciaran G. Morrison
Keyword(s):  
Calcium Binding ◽  
Primary Cilia ◽  
Reverse Genetics ◽  
Cell Types ◽  
Serum Starvation ◽  
Basal Bodies ◽  
Cilium Formation ◽  
Cellular Quiescence ◽  
Retinal Pigmented Epithelial Cells

Primary cilia are antenna-like sensory microtubule structures that extend from basal bodies, plasma membrane–docked mother centrioles. Cellular quiescence potentiates ciliogenesis, but the regulation of basal body formation is not fully understood. We used reverse genetics to test the role of the small calcium-binding protein, centrin2, in ciliogenesis. Primary cilia arise in most cell types but have not been described in lymphocytes. We show here that serum starvation of transformed, cultured B and T cells caused primary ciliogenesis. Efficient ciliogenesis in chicken DT40 B lymphocytes required centrin2. We disrupted CETN2 in human retinal pigmented epithelial cells, and despite having intact centrioles, they were unable to make cilia upon serum starvation, showing abnormal localization of distal appendage proteins and failing to remove the ciliation inhibitor CP110. Knockdown of CP110 rescued ciliation in CETN2-deficient cells. Thus, centrin2 regulates primary ciliogenesis through controlling CP110 levels.

Polaris, a protein disrupted inorpkmutant mice, is required for assembly of renal cilium

2002 ◽  
Vol 282 (3) ◽  
pp. F541-F552 ◽  
Author(s):  
Bradley K. Yoder ◽  
Albert Tousson ◽  
Leigh Millican ◽  
John H. Wu ◽  
Charles E. Bugg ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Collecting Duct ◽  
Physiological Role ◽  
Duct Cell ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Apical Surface ◽  
Cystic Disease ◽  
Cortical Collecting Duct

Cilia are organelles that play diverse roles, from fluid movement to sensory reception. Polaris, a protein associated with cystic kidney disease in Tg737°rpkmice, functions in a ciliogenic pathway. Here, we explore the role of polaris in primary cilia on Madin-Darby canine kidney cells. The results indicate that polaris localization and solubility change dramatically during cilia formation. These changes correlate with the formation of basal bodies and large protein rafts at the apical surface of the epithelia. A cortical collecting duct cell line has been derived from mice with a mutation in the Tg737 gene. These cells do not develop normal cilia, which can be corrected by reexpression of the wild-type Tg737 gene. These data suggest that the primary cilia are important for normal renal function and/or development and that the ciliary defect may be a contributing factor to the cystic disease in Tg737°rpkmice. Further characterization of these cells will be important in elucidating the physiological role of renal cilia and in determining their relationship to cystic disease.

scholarly journals The Role of Sonic Hedgehog in Human Holoprosencephaly and Short-Rib Polydactyly Syndromes

2021 ◽  
Vol 22 (18) ◽  
pp. 9854
Author(s):  
Christine Loo ◽  
Michael Pearen ◽  
Grant Ramm
Keyword(s):  
Human Development ◽  
Sonic Hedgehog ◽  
Mammalian Cells ◽  
Animal Studies ◽  
Primary Cilia ◽  
Genetic Mutation ◽  
Wide Variability ◽  
Using Data ◽  
Differentiation And Proliferation

The Hedgehog (HH) signalling pathway is one of the major pathways controlling cell differentiation and proliferation during human development. This pathway is complex, with HH function influenced by inhibitors, promotors, interactions with other signalling pathways, and non-genetic and cellular factors. Many aspects of this pathway are not yet clarified. The main features of Sonic Hedgehog (SHH) signalling are discussed in relation to its function in human development. The possible role of SHH will be considered using examples of holoprosencephaly and short-rib polydactyly (SRP) syndromes. In these syndromes, there is wide variability in phenotype even with the same genetic mutation, so that other factors must influence the outcome. SHH mutations were the first identified genetic causes of holoprosencephaly, but many other genes and environmental factors can cause malformations in the holoprosencephaly spectrum. Many patients with SRP have genetic defects affecting primary cilia, structures found on most mammalian cells which are thought to be necessary for canonical HH signal transduction. Although SHH signalling is affected in both these genetic conditions, there is little overlap in phenotype. Possible explanations will be canvassed, using data from published human and animal studies. Implications for the understanding of SHH signalling in humans will be discussed.

scholarly journals A Model for Primary Cilium Biogenesis by Polarized Epithelial Cells: Role of the Midbody Remnant and Associated Specialized Membranes

2021 ◽  
Vol 8 ◽  
Author(s):  
Leticia Labat-de-Hoz ◽  
Armando Rubio-Ramos ◽  
Javier Casares-Arias ◽  
Miguel Bernabé-Rubio ◽  
Isabel Correas ◽  
...  
Keyword(s):  
Cell Surface ◽  
Primary Cilium ◽  
Primary Cilia ◽  
Control Cell ◽  
Future Research ◽  
Alternative Route ◽  
Ciliary Membrane ◽  
Cilium Formation ◽  
Membrane Compartmentalization

Primary cilia are solitary, microtubule-based protrusions surrounded by a ciliary membrane equipped with selected receptors that orchestrate important signaling pathways that control cell growth, differentiation, development and homeostasis. Depending on the cell type, primary cilium assembly takes place intracellularly or at the cell surface. The intracellular route has been the focus of research on primary cilium biogenesis, whereas the route that occurs at the cell surface, which we call the “alternative” route, has been much less thoroughly characterized. In this review, based on recent experimental evidence, we present a model of primary ciliogenesis by the alternative route in which the remnant of the midbody generated upon cytokinesis acquires compact membranes, that are involved in compartmentalization of biological membranes. The midbody remnant delivers part of those membranes to the centrosome in order to assemble the ciliary membrane, thereby licensing primary cilium formation. The midbody remnant's involvement in primary cilium formation, the regulation of its inheritance by the ESCRT machinery, and the assembly of the ciliary membrane from the membranes originally associated with the remnant are discussed in the context of the literature concerning the ciliary membrane, the emerging roles of the midbody remnant, the regulation of cytokinesis, and the role of membrane compartmentalization. We also present a model of cilium emergence during evolution, and summarize the directions for future research.

scholarly journals Molecular Pathways and Therapies in Autosomal-Dominant Polycystic Kidney Disease

Physiology ◽  
2015 ◽  
Vol 30 (3) ◽  
pp. 195-207 ◽  
Author(s):  
Takamitsu Saigusa ◽  
P. Darwin Bell
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Primary Cilia ◽  
Autosomal Dominant ◽  
Molecular Pathways ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney ◽  
Multiple Cysts ◽  
Review Current

Autosomal-dominant polycystic kidney disease (ADPKD) is the most prevalent inherited renal disease, characterized by multiple cysts that can eventually lead to kidney failure. Studies investigating the role of primary cilia and polycystins have significantly advanced our understanding of the pathogenesis of PKD. This review will present clinical and basic aspects of ADPKD, review current concepts of PKD pathogenesis, evaluate potential therapeutic targets, and highlight challenges for future clinical studies.

Role of Ocrl1 in Primary Cilia Assembly

2015 ◽  
pp. 331-347 ◽  
Author(s):  
Kayalvizhi Madhivanan ◽  
Swetha Ramadesikan ◽  
R. Claudio Aguilar
Keyword(s):  
Primary Cilia

scholarly journals Primary cilium and glioblastoma

2018 ◽  
Vol 10 ◽  
pp. 175883591880116 ◽  
Author(s):  
María Álvarez-Satta ◽  
Ander Matheu
Keyword(s):  
Cancer Progression ◽  
Primary Cilium ◽  
Primary Cilia ◽  
Apical Surface ◽  
New Approach ◽  
Primary Brain Tumour ◽  
Tumorigenesis And Progression ◽  
Signalling Transduction ◽  
Abnormal Cilia

Glioblastoma (GBM) represents the most common, malignant and lethal primary brain tumour in adults. The primary cilium is a highly conserved and dynamic organelle that protrudes from the apical surface of virtually every type of mammalian cell. There is increasing evidence that abnormal cilia are involved in cancer progression, since primary cilia regulate cell cycle and signalling transduction. In this review, we summarize the role of primary cilium specifically with regard to GBM, where there is evidence postulating it as a critical mediator of GBM tumorigenesis and progression. This opens the way to the application of cilia-targeted therapies (‘ciliotherapy’) as a new approach in the fight against this devastating tumour.

scholarly journals Role of epidermal primary cilia in the homeostasis of skin and hair follicles

Development ◽  
2011 ◽  
Vol 138 (9) ◽  
pp. 1675-1685 ◽  
Author(s):  
M. J. Croyle ◽  
J. M. Lehman ◽  
A. K. O'Connor ◽  
S. Y. Wong ◽  
E. B. Malarkey ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Hair Follicles

268 ROLE OF ATPase MOTOR CYTOPLASMIC DYNEIN AND PRIMARY CILIA IN TESTICULAR MORPHOGENESIS

2015 ◽  
Vol 27 (1) ◽  
pp. 223
Author(s):  
C. Dores ◽  
I. Dobrinski
Keyword(s):  
Primary Cilia ◽  
Somatic Cells ◽  
Treated Group ◽  
Cytoplasmic Dynein ◽  
Control Group ◽  
Tubule Formation ◽  
Serum Free ◽  
Free Media

In vertebrates, the primary cilium is a nearly ubiquitous organelle present in somatic cells, but little is known about its function in the male gonad. We investigated the role of primary cilia in testis cells using in vitro formation of seminiferous tubules and in vitro culture of testicular somatic cells by inhibiting the primary cilium with CiliobrevinD, a cell-permeable, reversible chemical modulator that inhibits the major component of the organelle: ATPase motor cytoplasmic dynein. We analysed in vitro cultures for the presence of primary cilia and the activation of hedgehog signalling through translocation of Gli2 to the nuclei; in vitro tubule formation was evaluated by length and width of tubules formed. Methods: testicular cells were harvested from neonatal pigs by 2-step enzymatic digestion. Cells (50 × 106 mL–1) were plated on 100 mm Petri dishes in 15 mL of DMEM + 5% FBS + 50 U of penicillin and incubated at 37°C in 5% CO2 in air overnight, cells remaining in suspension and those slightly attached were removed and the somatic cells attached were trypsinized to obtain a single cell suspension, and then submitted to two different protocols: in vitro culture (A) or in vitro tubule formation (B), n = 5 replicates each. For A, somatic cells were replated on coverslips in 24-well plates and cultured in serum free media for 48 h, then for the treated group, 10 mM of CiliobrevinD was added for 24 h, attached cells from control and treated groups were fixed in 4% PFA and characterised by immunocytochemistry for ARL13B, Vimentin, and Gli2. For B: 1 × 106 cells were added to 24-well plates coated with 1 : 1 diluted Matrigel, the control group was kept in serum free media and to the treated group was added 20 mM CiliobrevinD at Day 0. Results: A) primary cilia were present in 89.3 ± 2.3% of cells cultured in serum-free media for the control group and Gli2 was located in the nuclei of 90.2 ± 1.2% of cells; in the CiliobrevinD-treated group the percentage of primary cilia decreased (P < 0.05) to 3.1 ± 2.5% and nuclear Gli2 to 3.9 ± 0.7; B) tubules formed in the control group were significantly longer and wider than the ones formed when CiliobrevinD was added (9.91 ± 0.35 v. 5.540 ± 1.08 mm and 339.8 ± 55.78 v. 127.2 ± 11.9 µm, respectively, P < 0.05 by Student's t-test). In conclusion, the inhibition of ATPase motor cytoplasmic dynein perturbs formation of primary cilia in testicular somatic cells, blocks Hedgehog signalling, and impairs in vitro tubule formation. Therefore, primary cilia on testicular somatic cells appear to be essential for testicular morphogenesis.Research was supported by 5 R01 OD016575-13.

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