scholarly journals The Caenorhabditis elegans nephrocystins act as global modifiers of cilium structure

2008 ◽  
Vol 180 (5) ◽  
pp. 973-988 ◽  
Author(s):  
Andrew R. Jauregui ◽  
Ken C.Q. Nguyen ◽  
David H. Hall ◽  
Maureen M. Barr
Keyword(s):  
Caenorhabditis Elegans ◽  
Intraflagellar Transport ◽  
Basal Bodies ◽  
Structural Components ◽  
Transition Zones ◽  
C Elegans ◽  
Cell Type Specific ◽  
Children And Young Adults ◽  
Stage Renal Disease ◽  
End Stage

Nephronophthisis (NPHP) is the most common genetic cause of end-stage renal disease in children and young adults. In Chlamydomonas reinhardtii, Caenorhabditis elegans, and mammals, the NPHP1 and NPHP4 gene products nephrocystin-1 and nephrocystin-4 localize to basal bodies or ciliary transition zones (TZs), but their function in this location remains unknown. We show here that loss of C. elegans NPHP-1 and NPHP-4 from TZs is tolerated in developing cilia but causes changes in localization of specific ciliary components and a broad range of subtle axonemal ultrastructural defects. In amphid channel cilia, nphp-4 mutations cause B tubule defects that further disrupt intraflagellar transport (IFT). We propose that NPHP-1 and NPHP-4 act globally at the TZ to regulate ciliary access of the IFT machinery, axonemal structural components, and signaling molecules, and that perturbing this balance results in cell type–specific phenotypes.

scholarly journals Functional Redundancy of the B9 Proteins and Nephrocystins in Caenorhabditis elegans Ciliogenesis

2008 ◽  
Vol 19 (5) ◽  
pp. 2154-2168 ◽  
Author(s):  
Corey L. Williams ◽  
Marlene E. Winkelbauer ◽  
Jenny C. Schafer ◽  
Edward J. Michaud ◽  
Bradley K. Yoder
Keyword(s):  
Caenorhabditis Elegans ◽  
Joubert Syndrome ◽  
Cystic Kidney ◽  
Basal Bodies ◽  
The Novel ◽  
C Elegans ◽  
Human Genes ◽  
Cilia Formation ◽  
Strong Candidate ◽  
Candidate Loci

Meckel-Gruber syndrome (MKS), nephronophthisis (NPHP), and Joubert syndrome (JBTS) are a group of heterogeneous cystic kidney disorders with partially overlapping loci. Many of the proteins associated with these diseases interact and localize to cilia and/or basal bodies. One of these proteins is MKS1, which is disrupted in some MKS patients and contains a B9 motif of unknown function that is found in two other mammalian proteins, B9D2 and B9D1. Caenorhabditis elegans also has three B9 proteins: XBX-7 (MKS1), TZA-1 (B9D2), and TZA-2 (B9D1). Herein, we report that the C. elegans B9 proteins form a complex that localizes to the base of cilia. Mutations in the B9 genes do not overtly affect cilia formation unless they are in combination with a mutation in nph-1 or nph-4, the homologues of human genes (NPHP1 and NPHP4, respectively) that are mutated in some NPHP patients. Our data indicate that the B9 proteins function redundantly with the nephrocystins to regulate the formation and/or maintenance of cilia and dendrites in the amphid and phasmid ciliated sensory neurons. Together, these data suggest that the human homologues of the novel B9 genes B9D2 and B9D1 will be strong candidate loci for pathologies in human MKS, NPHP, and JBTS.

scholarly journals Centrioles initiate cilia assembly but are dispensable for maturation and maintenance in C. elegans

2017 ◽  
Vol 216 (6) ◽  
pp. 1659-1671 ◽  
Author(s):  
Daniel Serwas ◽  
Tiffany Y. Su ◽  
Max Roessler ◽  
Shaohe Wang ◽  
Alexander Dammermann
Keyword(s):  
Fluorescence Microscopy ◽  
Transition Zone ◽  
Electron Tomography ◽  
Intraflagellar Transport ◽  
Basal Bodies ◽  
C Elegans ◽  
Cilia Formation ◽  
Syndrome Protein

Cilia are cellular projections that assemble on centriole-derived basal bodies. While cilia assembly is absolutely dependent on centrioles, it is not known to what extent they contribute to downstream events. The nematode C. elegans provides a unique opportunity to address this question, as centrioles do not persist at the base of mature cilia. Using fluorescence microscopy and electron tomography, we find that centrioles degenerate early during ciliogenesis. The transition zone and axoneme are not completely formed at this time, indicating that cilia maturation does not depend on intact centrioles. The hydrolethalus syndrome protein HYLS-1 is the only centriolar protein known to remain at the base of mature cilia and is required for intraflagellar transport trafficking. Surprisingly, targeted degradation of HYLS-1 after initiation of ciliogenesis does not affect ciliary structures. Taken together, our results indicate that while centrioles are essential to initiate cilia formation, they are dispensable for cilia maturation and maintenance.

Cardiac MRI assessment in children and young adults with end-stage renal disease

2018 ◽  
Vol 90 (3) ◽  
pp. 172-179
Author(s):  
Mary B. Avendt ◽  
Michael D. Taylor ◽  
Mark M. Mitsnefes
Keyword(s):  
Young Adults ◽  
Renal Disease ◽  
Cardiac Mri ◽  
End Stage Renal Disease ◽  
Children And Young Adults ◽  
Stage Renal Disease ◽  
End Stage

A cilia-mediated environmental input induces solitary behaviour in Caenorhabditis elegans and Pristionchus pacificus nematodes

Nematology ◽  
2018 ◽  
Vol 20 (3) ◽  
pp. 201-209 ◽  
Author(s):  
Eduardo Moreno ◽  
Ralf J. Sommer
Keyword(s):  
Caenorhabditis Elegans ◽  
Social Behaviour ◽  
Intraflagellar Transport ◽  
Large Protein ◽  
Pristionchus Pacificus ◽  
C Elegans ◽  
The Social ◽  
Genes Encoding ◽  
Social Behaviours ◽  
Ciliated Neurons

Nematodes respond to a multitude of environmental cues. For example, the social behaviours clumping and bordering were described as a mechanism of hyperoxia avoidance in Caenorhabditis elegans and Pristionchus pacificus. A recent study in P. pacificus revealed a novel regulatory pathway that inhibits social behaviour in a response to an as yet unknown environmental cue. This environmental signal is recognised by ciliated neurons, as mutants defective in intraflagellar transport (IFT) proteins display social behaviours. The IFT machinery represents a large protein complex and many mutants in genes encoding IFT proteins are available in C. elegans. However, social phenotypes in C. elegans IFT mutants have never been reported. Here, we examined 15 previously isolated C. elegans IFT mutants and found that most of them showed strong social behaviour. These findings indicate conservation in the inhibitory mechanism of social behaviour between P. pacificus and C. elegans.

scholarly journals Outcomes of Older Patients (≥60 years) with New-Onset Idiopathic Nephrotic Syndrome Receiving Immunosuppressive Regimen: A Multicentre Study of 116 Patients

2019 ◽  
Vol 8 (3) ◽  
pp. 298 ◽  
Author(s):  
Eloïse Colliou ◽  
Alexandre Karras ◽  
Jean-Jacques Boffa ◽  
David Ribes ◽  
Cyril Garrouste ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Cumulative Incidence ◽  
Older Patients ◽  
Idiopathic Nephrotic Syndrome ◽  
Kidney Injury ◽  
Renal Response ◽  
Children And Young Adults ◽  
Frontline Therapy ◽  
Stage Renal Disease ◽  
End Stage

Because of its rarity, renal presentation and outcomes of idiopathic nephrotic syndrome (INS; minimal changes disease or focal and segmental glomerulosclerosis) has poorly been described in elderly patients, precluding an individualized therapy procedure. Whether immunosuppressive regimens formerly designed in children and young adults are safe and efficient in elderly remains elusive. In a large multicentric retrospective study that included 116 patients with INS and onset ≥ 60 years of age, we showed that cumulative incidence of renal response was 95% after frontline therapy, with an age-dependent median time-to-response (60 days before 70 years of age at the onset vs. 120 days after; p = 0.03). Cumulative incidence of relapse was 90% at 7 years, with relapse occurring continuously over time. After a median follow-up of 34 months (IQR (12; 57)), 7 patients had died (6%) and 5 reached end-stage renal disease. Complications were highly prevalent: diabetes mellitus (23.3%), hypertension (24.1%), infection requiring hospitalization (21.6%) and acute kidney injury (9.5%). Thus, in older patients with INS and receiving steroids, renal response is delayed and relapse is the rule. Alternative immunosuppressive regimens, including B-cells depleting agents as frontline therapy, should be tested in this subset of patients to improve the mid- to long-term outcomes.

A single-cell map for the transcriptomic signatures of peripheral blood mononuclear cells in end-stage renal disease

2019 ◽  
Author(s):  
Ting Luo ◽  
Fengping Zheng ◽  
Kang Wang ◽  
Yong Xu ◽  
Huixuan Xu ◽  
...  
Keyword(s):  
Single Cell ◽  
End Stage Renal Disease ◽  
Mononuclear Cells ◽  
Cell Types ◽  
Cell Type ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Cell Type Specific ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background Immune aberrations in end-stage renal disease (ESRD) are characterized by systemic inflammation and immune deficiency. The mechanistic understanding of this phenomenon remains limited. Methods We generated 12 981 and 9578 single-cell transcriptomes of peripheral blood mononuclear cells (PBMCs) that were pooled from 10 healthy volunteers and 10 patients with ESRD by single-cell RNA sequencing. Unsupervised clustering and annotation analyses were performed to cluster and identify cell types. The analysis of hallmark pathway and regulon activity was performed in the main cell types. Results We identified 14 leukocytic clusters that corresponded to six known PBMC types. The comparison of cells from ESRD patients and healthy individuals revealed multiple changes in biological processes. We noticed an ESRD-related increase in inflammation response, complement cascade and cellular metabolism, as well as a strong decrease in activity related to cell cycle progression in relevant cell types in ESRD. Furthermore, a list of cell type-specific candidate transcription factors (TFs) driving the ESRD-associated transcriptome changes was identified. Conclusions We generated a distinctive, high-resolution map of ESRD-derived PBMCs. These results revealed cell type-specific ESRD-associated pathways and TFs. Notably, the pooled sample analysis limits the generalization of our results. The generation of larger single-cell datasets will complement the current map and drive advances in therapies that manipulate immune cell function in ESRD.

Segregation of germ granules in living Caenorhabditis elegans embryos: cell-type-specific mechanisms for cytoplasmic localisation

Development ◽  
1996 ◽  
Vol 122 (4) ◽  
pp. 1303-1312 ◽  
Author(s):  
S.N. Hird ◽  
J.E. Paulsen ◽  
S. Strome
Keyword(s):  
Caenorhabditis Elegans ◽  
Laser Scanning ◽  
Daughter Cell ◽  
Laser Scanning Confocal Microscopy ◽  
P Granules ◽  
C Elegans ◽  
Scanning Confocal Microscopy ◽  
Germ Granules ◽  
Cell Type Specific ◽  
P Cells

Germ granules are ribonucleoprotein particles that are thought to function in germline specification in invertebrates and possibly in vertebrates. In Caenorhabditis elegans, these structures, termed P granules, are partitioned to the germline P cells during the early embryonic divisions. By injecting a fluorescently labelled anti-P-granule antibody into the C. elegans germline syncitium, we followed P-granule segregation in live embryos using laser-scanning confocal microscopy. We show that, in early P cells (P0 and P1), P-granule partitioning is achieved primarily by their migration through the cytoplasm towards the site of formation of the germline daughter cell. A different mechanism appears to operate in later P cells (P2 and P3): P granules associate with the nucleus and move with it toward the site of formation of the germline daughter cell, where they are then deposited. At each division, there is also disassembly or degradation of those P granules that remain in the cytoplasm destined for the somatic daughter cell. Microfilaments, microtubules and the product of the gene mes-1 are required for the normal pattern of P-granule segregation in P2.

Carotid artery thickness in children and young adults with end stage renal disease

2007 ◽  
Vol 22 (1) ◽  
pp. 109-116 ◽  
Author(s):  
Hakan M. Poyrazoğlu ◽  
Ruhan Düşünsel ◽  
Ali Yıkılmaz ◽  
Nazmi Narin ◽  
Ruksan Anarat ◽  
...  
Keyword(s):  
Young Adults ◽  
Carotid Artery ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Children And Young Adults ◽  
Stage Renal Disease ◽  
End Stage

scholarly journals Incidence and causes of end-stage renal disease among Aboriginal children and young adults

2012 ◽  
Vol 184 (14) ◽  
pp. E758-E764 ◽  
Author(s):  
S. M. Samuel ◽  
B. J. Foster ◽  
B. R. Hemmelgarn ◽  
A. Nettel-Aguirre ◽  
L. Crowshoe ◽  
...  
Keyword(s):  
Young Adults ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Children And Young Adults ◽  
Stage Renal Disease ◽  
End Stage ◽  
Aboriginal Children

Intraflagellar transport motors in Caenorhabditis elegans neurons

2004 ◽  
Vol 32 (5) ◽  
pp. 682-684 ◽  
Author(s):  
J.M. Scholey ◽  
G. Ou ◽  
J. Snow ◽  
A. Gunnarson
Keyword(s):  
Caenorhabditis Elegans ◽  
Fluorescent Protein ◽  
Protein Complexes ◽  
Intraflagellar Transport ◽  
Time Lapse ◽  
Protein Fusion ◽  
C Elegans ◽  
Sensory Cilia ◽  
Macromolecular Protein ◽  
Green Fluorescent

IFT (intraflagellar transport) assembles and maintains sensory cilia on the dendritic endings of chemosensory neurons within the nematode Caenorhabditis elegans. During IFT, macromolecular protein complexes called IFT particles (which carry ciliary precursors) are moved from the base of the sensory cilium to its distal tip by anterograde IFT motors (kinesin-II and Osm-3 kinesin) and back to the base by retrograde IFT-dynein [Rosenbaum and Witman (2002) Nat. Rev. Mol. Cell Biol. 3, 813–825; Scholey (2003) Annu. Rev. Cell Dev. Biol. 19, 423–443; and Snell, Pan and Wang (2004) Cell 117, 693–697]. In the present study, we describe the protein machinery of IFT in C. elegans, which we have analysed using time-lapse fluorescence microscopy of green fluorescent protein-fusion proteins in concert with ciliary mutants.

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