scholarly journals Osteoarthritis-Like Changes in Bardet–Biedl Syndrome Mutant Ciliopathy Mice (Bbs1M390R/M390R): Evidence for a Role of Primary Cilia in Cartilage Homeostasis and Regulation of Inflammation

2018 ◽  
Vol 9 ◽  
Author(s):  
Isaac D. Sheffield ◽  
Mercedes A. McGee ◽  
Steven J. Glenn ◽  
Da Young Baek ◽  
Joshua M. Coleman ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Bardet Biedl Syndrome ◽  
Cartilage Homeostasis

scholarly journals Small Noncoding RNAs in Knee Osteoarthritis: The Role of MicroRNAs and tRNA-Derived Fragments

2021 ◽  
Vol 22 (11) ◽  
pp. 5711
Author(s):  
Julian Zacharjasz ◽  
Anna M. Mleczko ◽  
Paweł Bąkowski ◽  
Tomasz Piontek ◽  
Kamilla Bąkowska-Żywicka
Keyword(s):  
Knee Osteoarthritis ◽  
Noncoding Rnas ◽  
Pathological Process ◽  
Joint Disease ◽  
Limited Information ◽  
Genetic Changes ◽  
Small Noncoding Rnas ◽  
Knee Oa ◽  
Cartilage Homeostasis

Knee osteoarthritis (OA) is a degenerative knee joint disease that results from the breakdown of joint cartilage and underlying bone, affecting about 3.3% of the world's population. As OA is a multifactorial disease, the underlying pathological process is closely associated with genetic changes in articular cartilage and bone. Many studies have focused on the role of small noncoding RNAs in OA and identified numbers of microRNAs that play important roles in regulating bone and cartilage homeostasis. The connection between other types of small noncoding RNAs, especially tRNA-derived fragments and knee osteoarthritis is still elusive. The observation that there is limited information about small RNAs different than miRNAs in knee OA was very surprising to us, especially given the fact that tRNA fragments are known to participate in a plethora of human diseases and a portion of them are even more abundant than miRNAs. Inspired by these findings, in this review we have summarized the possible involvement of microRNAs and tRNA-derived fragments in the pathology of knee osteoarthritis.

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.

Molecular genetic diagnostics of Bardet-Biedl syndrome with an MPS-panel

2021 ◽  
pp. 26-35
Author(s):  
М.Д. Орлова ◽  
П. Гундорова ◽  
А.В. Поляков
Keyword(s):  
Autosomal Recessive ◽  
Molecular Genetic ◽  
Autosomal Recessive Disorder ◽  
Genetic Diagnostics ◽  
Bardet Biedl Syndrome ◽  
Pathogenic Variants ◽  
Development Delay ◽  
Molecular Genetic Diagnostics ◽  
First Time

Синдром Барде-Бидля - аутосомно-рецессивное заболевание, характеризующееся ожирением, пигментной дегенерацией сетчатки, полидактилией, задержкой психоречевого развития и структурными повреждениями почек. В работе представлены результаты применения МПС-панели, включающей кодирующие последовательности и прилегающие интронные области 21 гена, ассоциированного с синдромом Барде-Бидля. Впервые была проведена молекулярно-генетическая диагностика в группе из сорока российских пациентов с синдромом Барде-Бидля из неродственных семей. В результате исследования удалось подтвердить диагноз молекулярно-генетическим методом у 40% пациентов (n=16). В генах BBS1, BBS7 и BBS10 встретились повторяющиеся варианты. Частота встречаемости патогенных и вероятно патогенных вариантов в генах BBS1 и BBS10 у российских пациентов соответствует зарубежным данным. Варианты в гене BBS7 встретились у пяти человек, у четырех из них был обнаружен патогенный вариант c.1967_1968delTAinsC, не встречающийся в других популяциях. Результаты, представленные в статье, показывают значительный вклад в заболеваемость синдромом Барде-Бидля в российской популяции патогенных вариантов в гене BBS7. Bardet-Biedl syndrome is an autosomal recessive disorder characterized by obesity, retinitis pigmentosa, polydactyly, development delay, and structural kidney defects. This study shows the results of using an MPS panel that includes coding sequences and intronic areas of 21 genes associated with Bardet-Biedl syndrome. For the first time molecular genetic testing has been provided for the group of 40 Russian patiens with Bardet-Biedl syndrome from unrelated families. As a result of the testing, diagnoses were confirmed for 40% of the patients (n=16). The genes BBS1, BBS7, BBS10 had recurrent variants. The frequency of pathogenic and likely pathogenic variants in the genes BBS1 and BBS10 among Russian patients matches the research data in other countries. Variants in the BBS7 gene were found for five people, four of them had a pathogenic variant c.1967_1968delTAinsC, which is not present among other populations. Results provided in this article show the significant role of pathogenic variants in the BBS7 gene in patients with Bardet-Biedl syndrome in Russian population.

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.

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