NDP kinase moves into developing primary cilia

Mitchell, Kimberly A. P.; Gallagher, Betty C.; Szabó, Gábor; Otero, Angela de S.

doi:10.1002/cm.20025

Cited by 14 publications

(20 citation statements)

References 47 publications

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“…b, electron micrograph of isolated cilia. Arrowheads and arrows indicate cilia and cilia tip structures, respectively, consistent with previous reports (26). Right panels detail cilia and tips.…”

Section: Discussionsupporting

confidence: 89%

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Characterization of Single Channel Currents from Primary Cilia of Renal Epithelial Cells

Raychowdhury

McLaughlin

Ramos

et al. 2005

Journal of Biological Chemistry

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The primary cilium is a ubiquitous, non-motile microtubular organelle lacking the central pair of microtubules found in motile cilia. Primary cilia are surrounded by a membrane, which has a unique complement of membrane proteins, and may thus be functionally different from the plasma membrane. The function of the primary cilium remains largely unknown. However, primary cilia have important sensory transducer properties, including the response of renal epithelial cells to fluid flow or mechanical stimulation. Recently, renal cystic diseases have been associated with dysfunctional ciliary proteins. Although the sensory properties of renal epithelial primary cilia may be associated with functional channel activity in the organelle, information in this regard is still lacking. This may be related to the inherent difficulties in assessing electrical activity in this rather small and narrow organelle. In the present study, we provide the first direct electrophysiological evidence for the presence of single channel currents from isolated primary cilia of LLC-PK1 renal epithelial cells. Several channel phenotypes were observed, and addition of vasopressin increased cation channel activity, which suggests the regulation, by the cAMP pathway of ciliary conductance. Ion channel reconstitution of ciliary versus plasma membranes indicated a much higher channel density in cilia. At least three channel proteins, polycystin-2, TRPC1, and interestingly, the ␣-epithelial sodium channel, were immunodetected in this organelle. Ion channel activity in the primary cilium of renal cells may be an important component of its role as a sensory transducer.

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Section: Discussionsupporting

confidence: 89%

“…Isolated cilia were further visualized and identified at higher resolution (ϫ25,000) by electron microscopy (Fig. 2b) where ciliary stems and tips can be identified as reported (26).…”

Section: Identification and Isolation Of Primary Cilia From Llc-pk1 Cmentioning

confidence: 99%

Characterization of Single Channel Currents from Primary Cilia of Renal Epithelial Cells

Raychowdhury

McLaughlin

Ramos

et al. 2005

Journal of Biological Chemistry

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“…If this is to be investigated in cells in culture or tissues by means other than, or in addition to, fluorescence microscopy, then it would be helpful to have efficient methods for the isolation of primary cilia and, in turn, ciliary membranes from these cells. Although methods for doing this have been published, it is technically demanding, and only small amounts of cilia are obtained [51,52]. …”

Section: Introductionmentioning

confidence: 99%

Intraflagellar transport: it's not just for cilia anymore

Baldari

Rosenbaum

2010

Current Opinion in Cell Biology

106

100

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Recently-published information on the role of IFT polypeptides in vesicle exocytosis is reviewed, describing the formation of the immune synapse in non -ciliated cells as an example. An hypothesis is detailed suggesting that all polypeptides which enter the cilium, both membrane and axonemal, do so in association, first, with cytoplasmic vesicles which exocytose adjacent to the ciliary basal body, and then with the ciliary membrane. Axonemal proteins are moved to the ciliary tip by peripheral association with the inner aspects of the ciliary membrane by cannonical ciliary IFT. At the tip, some polypeptides are released for axonemal assembly, and others are budded off as part of vesicular exosomes into the environment. It is proposed that the cilium, in addition to being a sensory and motile organelle, is also a secretory organelle.

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“…Just recently, these two thioredoxins have been involved in the control of flagellar motility through their interactions with flagellar components (41). In addition, from Chlamydomonas to mammals, NDP kinases are also found in ciliary structures where they are supposed to play essential functions, particularly through their ability to produce GTP (42)(43)(44). Taken together, these observations strongly support ., pTXNDC3C 1, pTXNDC3C2, pTXNDC3T1ϾC, and pTXNDC3T2ϾC) or a thymine at that position (i.e., pTXNDC3T 1, pTXNDC3T2, pTXNDC3C1ϾT, and pTXNDC3C 2ϾT) (see Materials and Methods).…”

Section: Presumed Functions Of Human Txndc3 Isoforms In Light Of Theirmentioning

confidence: 66%

A common variant in combination with a nonsense mutation in a member of the thioredoxin family causes primary ciliary dyskinesia

Duriez

Duquesnoy

Escudier

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

176

101

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Thioredoxins belong to a large family of enzymatic proteins that function as general protein disulfide reductases, therefore participating in several cellular processes via redox-mediated reactions. So far, none of the 18 members of this family has been involved in human pathology. Here we identified TXNDC3 , which encodes a thioredoxin–nucleoside diphosphate kinase, as a gene implicated in primary ciliary dyskinesia (PCD), a genetic condition characterized by chronic respiratory tract infections, left–right asymmetry randomization, and male infertility. We show that the disease, which segregates as a recessive trait, results from the unusual combination of the following two transallelic defects: a nonsense mutation and a common intronic variant found in 1% of control chromosomes. This variant affects the ratio of two physiological TXNDC3 transcripts: the full-length isoform and a novel isoform, TXNDC3d7 , carrying an in-frame deletion of exon 7. In vivo and in vitro expression data unveiled the physiological importance of TXNDC3d7 (whose expression was reduced in the patient) and the corresponding protein that was shown to bind microtubules. PCD is known to result from defects of the axoneme, an organelle common to respiratory cilia, embryonic nodal cilia, and sperm flagella, containing dynein arms, with, to date, the implication of genes encoding dynein proteins. Our findings, which identify a another class of molecules involved in PCD, disclose the key role of TXNDC3 in ciliary function; they also point to an unusual mechanism underlying a Mendelian disorder, which is an SNP-induced modification of the ratio of two physiological isoforms generated by alternative splicing.

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NDP kinase moves into developing primary cilia

Cited by 14 publications

References 47 publications

Characterization of Single Channel Currents from Primary Cilia of Renal Epithelial Cells

Characterization of Single Channel Currents from Primary Cilia of Renal Epithelial Cells

Intraflagellar transport: it's not just for cilia anymore

A common variant in combination with a nonsense mutation in a member of the thioredoxin family causes primary ciliary dyskinesia

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