Cilia and polycystic kidney disease, kith and kin

Huang, Liwei; Lipschutz, Joshua H.

doi:10.1002/bdrc.21066

Cited by 21 publications

(15 citation statements)

References 96 publications

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“…Release of these vesicles into the extracellular space is mediated by budding of the plasma membrane at the ciliary base 36. The exocyst complex might also play a role in migration, planar positioning and docking of the cilium basal body by targeting ciliary vesicles to the plasma membrane 37. Therefore, it is not surprising that mutations in two exocyst components have been shown to cause ciliopathies 38 39.…”

Section: Discussionmentioning

confidence: 99%

Biallelic mutations in EXOC3L2 cause a novel syndrome that affects the brain, kidney and blood

et al. 2018

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BackgroundDandy-Walker malformation features agenesis/hypoplasia of the cerebellar vermis, cystic dilatation of the fourth ventricle and enlargement of posterior fossa. Although Dandy-Walker malformation is relatively common and several genes were linked to the syndrome, the genetic cause in the majority of cases is unknown.ObjectiveTo identify the mutated gene responsible for Dandy-Walker malformation, kidney disease and bone marrow failure in four patients from two unrelated families.MethodsMedical assessment, sonographic, MRI and pathological studies were used to define phenotype. Chromosomal microarray analysis and whole-exome sequence were performed to unravel the genotype.ResultsWe report four subjects from two unrelated families with homozygous mutations in the Exocyst Complex Component 3-Like-2 gene (EXOC3L2).EXOC3L2 functions in trafficking of post-Golgi vesicles to the plasma membrane. In the first family a missense mutation in a highly conserved amino acid, p.Leu41Gln, was found in three fetuses; all had severe forms of Dandy-Walker malformation that was detectable by prenatal ultrasonography and confirmed by autopsy. In the second family, the affected child carried a nonsense mutation, p.Arg72*, and no detected protein. He had peritrigonal and cerebellar white matter abnormalities with enlargement of the ventricular trigones, developmental delay, pituitary hypoplasia, severe renal dysplasia and bone marrow failure.ConclusionWe propose that biallelic EXOC3L2 mutations lead to a novel syndrome that affects hindbrain development, kidney and possibly the bone marrow.

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Section: Discussionmentioning

confidence: 99%

Biallelic mutations in EXOC3L2 cause a novel syndrome that affects the brain, kidney and blood

et al. 2018

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“…As mutations in either PKD1 or PKD2 cause autosomal dominant polycystic kidney disease (ADPKD) in humans (FIG. 3; see Supplementary information S1 (table)), decreased ciliary localization of PKD2 may account for the kidney cysts in MKS 103 . Therefore, although it is possible to build cilia without a transition zone 9,99 , transition zone-associated ciliopathies are probably the result of the altered distribution of one or more ciliary signalling proteins.…”

Section: Transition Zone Is a Hotspot For Ciliopathiesmentioning

confidence: 99%

Genes and molecular pathways underpinning ciliopathies

Reiter

Leroux

2017

Nat Rev Mol Cell Biol

1,233

1,237

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Motile and non-motile (primary) cilia are nearly ubiquitous cellular organelles. The dysfunction of cilia causes diseases known as ciliopathies. The number of reported ciliopathies (currently 35) is increasing, as is the number of established (187) and candidate (241) ciliopathy-associated genes. The characterization of ciliopathy-associated proteins and phenotypes has improved our knowledge of ciliary functions. In particular, investigating ciliopathies has helped us to understand the molecular mechanisms by which the cilium-associated basal body functions in early ciliogenesis, as well as how the transition zone functions in ciliary gating, and how intraflagellar transport enables cargo trafficking and signalling. Both basic biological and clinical studies are uncovering novel ciliopathies and the ciliary proteins involved. The assignment of these proteins to different ciliary structures, processes and ciliopathy subclasses (first order and second order) provides insights into how this versatile organelle is built, compartmentalized and functions in diverse ways that are essential for human health.

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“…In some respect this ciliary vesicle/centrosome interaction is similar to the endosome/centrosome interaction mentioned above (Hehnly et al, 2012 ). By targeting the ciliary vesicle toward the PM, the exocyst may therefore participate in the migration, planar positioning or docking of the basal body (Park et al, 2008 ; Huang and Lipschutz, 2014 ).…”

Section: The Exocyst Complex In Metazoamentioning

confidence: 99%

The Exocyst Complex in Health and Disease

Martín-Urdiroz

Deeks

Horton

et al. 2016

Front. Cell Dev. Biol.

103

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Exocytosis involves the fusion of intracellular secretory vesicles with the plasma membrane, thereby delivering integral membrane proteins to the cell surface and releasing material into the extracellular space. Importantly, exocytosis also provides a source of lipid moieties for membrane extension. The tethering of the secretory vesicle before docking and fusion with the plasma membrane is mediated by the exocyst complex, an evolutionary conserved octameric complex of proteins. Recent findings indicate that the exocyst complex also takes part in other intra-cellular processes besides secretion. These various functions seem to converge toward defining a direction of membrane growth in a range of systems from fungi to plants and from neurons to cilia. In this review we summarize the current knowledge of exocyst function in cell polarity, signaling and cell-cell communication and discuss implications for plant and animal health and disease.

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Cilia and polycystic kidney disease, kith and kin

Cited by 21 publications

References 96 publications

Biallelic mutations in EXOC3L2 cause a novel syndrome that affects the brain, kidney and blood

Biallelic mutations in EXOC3L2 cause a novel syndrome that affects the brain, kidney and blood

Genes and molecular pathways underpinning ciliopathies

The Exocyst Complex in Health and Disease

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