Novel regulators of primary cilium function revealed by molecular studies in ciliopathies

2016 ◽  
Author(s):  
Claudio Rodrigo David Cortés Rodríguez
Keyword(s):  
Primary Cilium ◽  
Molecular Studies ◽  
Cilium Function

scholarly journals Deficiency of U4atac snRNA secondarily results in ciliary defects

2021 ◽  
Author(s):  
Deepak Khatri ◽  
Audrey Putoux ◽  
Audric Cologne ◽  
Sophie Kaltenbach ◽  
Alicia Besson ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Primary Cilium ◽  
Growth Retardation ◽  
Skeletal Dysplasia ◽  
Developmental Disorders ◽  
Retinal Dystrophy ◽  
Joubert Syndrome ◽  
Zebrafish Model ◽  
Splicing Defects ◽  
Cilium Function

In the human genome, about 700 genes contain usually one intron excised by the minor spliceosome. This spliceosome comprises its own set of snRNAs, among which U4atac. Its non-coding gene, RNU4ATAC, has been found mutated in Taybi-Linder (MOPD1/TALS), Roifman (RFMN) and Lowry-Wood syndromes (LWS). These rare developmental disorders, whose physiopathological mechanisms remain unsolved, associate ante- and post-natal growth retardation, microcephaly, skeletal dysplasia, intellectual disability, retinal dystrophy and immunodeficiency. Here, we report a homozygous RNU4ATAC mutation in the Stem II domain, n.16G>A, in two unrelated patients presenting with both typical traits of the Joubert syndrome (JBTS), a well-characterized ciliopathy, and of TALS/RFMN/LWS, thus widening the clinical spectrum of RNU4ATAC-associated disorders and indicating ciliary dysfunction as a mechanism downstream of minor splicing defects. This finding is supported by alterations of primary cilium function in TALS and JBTS/RFMN fibroblasts, as well as by u4atac zebrafish model, which exhibit ciliopathy-related phenotypes and ciliary defects. Altogether, our data indicate that alteration of cilium biogenesis is part of the physiopathological mechanisms of TALS/RFMN/LWS, secondarily to defects of minor intron splicing.

scholarly journals PI3K Class II α Controls Spatially Restricted Endosomal PtdIns3P and Rab11 Activation to Promote Primary Cilium Function

2014 ◽  
Vol 28 (6) ◽  
pp. 647-658 ◽  
Author(s):  
Irene Franco ◽  
Federico Gulluni ◽  
Carlo C. Campa ◽  
Carlotta Costa ◽  
Jean Piero Margaria ◽  
...  
Keyword(s):  
Primary Cilium ◽  
Class Ii ◽  
Cilium Function

scholarly journals The centriolar satellite proteins Cep72 and Cep290 interact and are required for recruitment of BBS proteins to the cilium

2012 ◽  
Vol 23 (17) ◽  
pp. 3322-3335 ◽  
Author(s):  
Timothy R. Stowe ◽  
Christopher J. Wilkinson ◽  
Anila Iqbal ◽  
Tim Stearns
Keyword(s):  
Primary Cilium ◽  
Protein Trafficking ◽  
Interacting Protein ◽  
Centrosomal Protein ◽  
Cilium Function ◽  
Ciliary Localization

Defects in centrosome and cilium function are associated with phenotypically related syndromes called ciliopathies. Centriolar satellites are centrosome-associated structures, defined by the protein PCM1, that are implicated in centrosomal protein trafficking. We identify Cep72 as a PCM1-interacting protein required for recruitment of the ciliopathy-associated protein Cep290 to centriolar satellites. Loss of centriolar satellites by depletion of PCM1 causes relocalization of Cep72 and Cep290 from satellites to the centrosome, suggesting that their association with centriolar satellites normally restricts their centrosomal localization. We identify interactions between PCM1, Cep72, and Cep290 and find that disruption of centriolar satellites by overexpression of Cep72 results in specific aggregation of these proteins and the BBSome component BBS4. During ciliogenesis, BBS4 relocalizes from centriolar satellites to the primary cilium. This relocalization occurs normally in the absence of centriolar satellites (PCM1 depletion) but is impaired by depletion of Cep290 or Cep72, resulting in defective ciliary recruitment of the BBSome subunit BBS8. We propose that Cep290 and Cep72 in centriolar satellites regulate the ciliary localization of BBS4, which in turn affects assembly and recruitment of the BBSome. Finally, we show that loss of centriolar satellites in zebrafish leads to phenotypes consistent with cilium dysfunction and analogous to those observed in human ciliopathies.

Growth factors and the primary cilium in BALB/c 3T3 cells

1987 ◽  
Vol 45 ◽  
pp. 830-831
Author(s):  
R. W. Tucker ◽  
N. S. More ◽  
S. Jayaraman
Keyword(s):  
Growth Factors ◽  
Primary Cilium ◽  
Cultured Cells ◽  
Morphological Changes ◽  
Calcium Ionophore ◽  
Growth Stimulation ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
3T3 Cells ◽  
Microtubule Depolymerization

The mechanisms by which polypeptide growth factors Induce DNA synthesis in cultured cells is not understood, but morphological changes Induced by growth factors have been used as clues to Intracellular messengers responsible for growth stimulation. One such morphological change has been the transient disappearance of the primary cilium, a “9 + 0” cilium formed by the perinuclear centriole in interphase cells. Since calcium ionophore A23187 also produced both mitogenesis and ciliary changes, microtubule depolymerization might explain ciliary disappearance monitored by indirect immunofluorescence with anti-tubulin antibody. However, complete resorption and subsequent reformation of the primary cilium occurs at mitosis, and might also account for ciliary disappearance induced by growth factors. To settle this issue, we investigated the ultrastructure of the primary cilium using serial thin-section electron microscopy of quiescent BALB/c 3T3 cells before and after stimulation with serum.

Darwin's two competing phylogenetic trees: marsupials as ancestors or sister taxa?

2012 ◽  
Vol 39 (2) ◽  
pp. 217-233 ◽  
Author(s):  
J. David Archibald
Keyword(s):  
Fossil Record ◽  
Evolutionary Biology ◽  
Phylogenetic Trees ◽  
Charles Darwin ◽  
The Other ◽  
Charles Lyell ◽  
Single Origin ◽  
Molecular Studies ◽  
Richard Owen ◽  
First Time

Studies of the origin and diversification of major groups of plants and animals are contentious topics in current evolutionary biology. This includes the study of the timing and relationships of the two major clades of extant mammals – marsupials and placentals. Molecular studies concerned with marsupial and placental origin and diversification can be at odds with the fossil record. Such studies are, however, not a recent phenomenon. Over 150 years ago Charles Darwin weighed two alternative views on the origin of marsupials and placentals. Less than a year after the publication of On the origin of species, Darwin outlined these in a letter to Charles Lyell dated 23 September 1860. The letter concluded with two competing phylogenetic diagrams. One showed marsupials as ancestral to both living marsupials and placentals, whereas the other showed a non-marsupial, non-placental as being ancestral to both living marsupials and placentals. These two diagrams are published here for the first time. These are the only such competing phylogenetic diagrams that Darwin is known to have produced. In addition to examining the question of mammalian origins in this letter and in other manuscript notes discussed here, Darwin confronted the broader issue as to whether major groups of animals had a single origin (monophyly) or were the result of “continuous creation” as advocated for some groups by Richard Owen. Charles Lyell had held similar views to those of Owen, but it is clear from correspondence with Darwin that he was beginning to accept the idea of monophyly of major groups.

On Riccia marginata and related species (Ricciaceae, Marchantiophyta)

2012 ◽  
Vol 46 ◽  
pp. 298-305 ◽  
Author(s):  
A. D. Potemkin ◽  
T. Ahti
Keyword(s):  
Related Species ◽  
Lake Ladoga ◽  
Leningrad Region ◽  
Sem Images ◽  
North Shore ◽  
The North ◽  
Molecular Studies ◽  
The Future ◽  
The Town

Riccia marginata Lindb. was described by S. O. Lindberg (1877) from the outskirts of the town of Sortavala near the north shore of Lake Ladoga, Republic of Karelia, Russia. The species has been forgotten in most recent liverwort accounts of Europe, including Russia. Lectotypification of R. marginata is provided. R. marginata shares most characters with R. beyrichiana Hampe ex Lehm. It differs from “typical” plants of R. beyrichiana in having smaller spores, with ± distinctly finely areolate to roughly papillose proximal surfaces and a narrower and shorter thallus, as well as in scarcity or absence of marginal hairs. It may represent continental populations of the suboceanic-submediterranean R. beyrichiana, known in Russia from the Leningrad Region and Karelia only. The variability of spore surfaces in R. beyrichiana is discussed and illustrated by SEM images. A comparison with the spores of R. bifurca Hoffm. is provided. The question how distinct R. marginata is from R. beyrichiana needs to be clarified by molecular studies in the future, when adequate material is available. R. marginata is for the time being, provisionally, included in R. beyrichiana.

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