Nephrocystin interacts with Pyk2, p130
            <sup>Cas</sup>
            , and tensin and triggers phosphorylation of Pyk2

Benzing, Thomas; Gerke, Peter; Höpker, Katja; Hildebrandt, Friedhelm; Kim, Emily; Walz, Gerd

doi:10.1073/pnas.171269898

Cited by 108 publications

(98 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, nephrocystin has been described as a novel docking protein [10][11][12][13] that interacts with components of cell-cell and cell-matrix signaling, such as focal adhesion kinase 2, tensin, p130Cas, filamin and nephrocystin-4 or nephroretinin 7 . These observations suggest that proteins associated with renal cystic disease may have multiple functions depending on their localization in different cell compartments and their association with distinct protein assemblies.…”

Section: Discussionmentioning

confidence: 99%

“…FLAG-tagged versions of nephrocystin have been described 13 . J. Goodship (University of Newcastle, UK) provided mouse Invs cDNA.…”

Section: Plasmidsmentioning

confidence: 99%

“…After centrifugation to remove cellular debris, we subjected the supernatant to ultracentrifugation (100,000g) for 30 min followed by extensive preclearing with protein Gsepharose. We then carried out immunoprecipitation with control antibody or nephrocystin antiserum as recently described 13 .…”

Section: Coimmunoprecipitationmentioning

confidence: 99%

“…4,5). It encodes a novel docking protein, nephrocystin [10][11][12][13] , that interacts with components of cell-cell and cell-matrix signaling, such as focal adhesion kinase 2, tensin, p130Cas and filamin, and with nephrocystin-4 or nephroretinin, the product of NPHP4, mutations in which cause NPHP4 (OMIM 606966; refs. 6,7).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination

et al. 2003

Self Cite

View full text Add to dashboard Cite

Nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, leads to chronic renal failure in children. The genes mutated in NPHP1 and NPHP4 have been identified, and a gene locus associated with infantile nephronophthisis (NPHP2) was mapped. The kidney phenotype of NPHP2 combines clinical features of NPHP and polycystic kidney disease (PKD). Here, we identify inversin (INVS) as the gene mutated in NPHP2 with and without situs inversus. We show Correspondence should be addressed to F.H. (fhilde@umich.edu). 12 These authors contributed equally to this work 13 These authors contributed equally to this work GenBank accession numbers. INVS cDNA, NM_014425; Invs cDNA, NM_010569; invs cDNA, AF465261; INVS in chromosome 9 genome contig, NT_008470.URLs. Additional information is available at http://danio.mgh.harvard.edu/blast/blast.html. Note: Supplementary information is available on the Nature Genetics website. Competing Interests Statement:The authors declare that they have no competing financial interests. NIH Public AccessAuthor Manuscript Nat Genet. Author manuscript; available in PMC 2013 August 02. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript molecular interaction of inversin with nephrocystin, the product of the gene mutated in NPHP1 and interaction of nephrocystin with β-tubulin, a main component of primary cilia. We show that nephrocystin, inversin and β-tubulin colocalize to primary cilia of renal tubular cells. Furthermore, we produce a PKD-like renal cystic phenotype and randomization of heart looping by knockdown of invs expression in zebrafish. The interaction and colocalization in cilia of inversin, nephrocystin and β-tubulin connect pathogenetic aspects of NPHP to PKD, to primary cilia function and to leftright axis determination.NPHP, an autosomal recessive cystic kidney disease, is the most frequent genetic cause for end-stage renal failure in children and young adults [1][2][3] . Causative mutations in two genes (NPHP1 and NPHP4) have been identified by positional cloning [4][5][6][7] . There is considerable interest in identifying genes associated with NPHP because its most prominent feature is development of renal interstitial fibrosis 8 , which in chronic renal disease of all origin represents the pathogenic event correlated most strongly to loss of renal function 9 . As little was known about the pathogenesis of NPHP, positional cloning was used to identify a new gene, NPHP1, mutations in which cause NPHP1 (OMIM 256100; refs. 4,5). It encodes a novel docking protein, nephrocystin [10][11][12][13] , that interacts with components of cell-cell and cell-matrix signaling, such as focal adhesion kinase 2, tensin, p130Cas and filamin, and with nephrocystin-4 or nephroretinin, the product of NPHP4, mutations in which cause NPHP4 (OMIM 606966; refs. 6,7). Identification of the genes NPHP1 and NPHP4, which are conserved in evolution including in the nematode Caenorhabditis elegans, offered new insights into mechanisms of cell-cell and cell-matrix signaling...

show abstract

Section: Discussionmentioning

confidence: 99%

“…FLAG-tagged versions of nephrocystin have been described 13 . J. Goodship (University of Newcastle, UK) provided mouse Invs cDNA.…”

Section: Plasmidsmentioning

confidence: 99%

Section: Coimmunoprecipitationmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination

et al. 2003

Self Cite

View full text Add to dashboard Cite

show abstract

“…In part, this is because we do not yet know the function of fibrocystin (the protein encoded by the autosomal recessive PKD gene) or of any of the four nephronopthisis genes. Nephrocystin 4 in mouse has been linked to signal transduction proteins, such as protein tyrosine kinases, 82,83 but whether this interaction occurs in cilia and how the interaction relates to its function is unknown. Several of the PKD gene products are also associated with other cilia-related disorders.…”

Section: Cilia-related Disorders J Pan Et Almentioning

confidence: 99%

Cilium-generated signaling and cilia-related disorders

Pan

Wang

Snell

2005

Laboratory Investigation

211

183

View full text Add to dashboard Cite

Biologists have long known that humans experience their environment through cilia. Light, odorant, and sound perception depend on these microtubule-filled, complex organelles present on cells in primary sensory tissues. Recently, discoveries on the mechanism of assembly of cilia (flagella) in the lowly, biflagellated, eucaryotic green alga Chlamydomonas have triggered a renaissance of interest in the organelles along with a recognition of their key sensory roles in nonsensory tissues. Chlamydomonas researchers uncovered an entirely new set of cellular machinery essential for transporting the protein components of cilia and flagella in all ciliated/ flagellated eukaryotic cells between their site of synthesis in the cell body and their site of assembly at the tip of the flagellum (intraflagellar transport: IFT). Prompted by the surprising observations that disruption of IFT genes in mice led to polycystic kidney disease (PKD) and that PKD proteins are present on the sensory cilia of Caenorhabditis elegans, researchers have made a direct connection between PKD and cilia. At least five (and possibly all) of the seven identified human genes disrupted in PKD and a related disorder nephronophthisis encode proteins expressed in the primary cilia that project into the lumen from the epithelial cells that line renal tubules. Moreover, the renal cilia are flow sensors and at least two of the PKD genes encode ciliary transmembrane proteins essential for mechanosensation. Although their roles have not yet been as clearly identified, cilia also are at the center of a rare human disorder, Bardet-Biedl syndrome (BBS), in which patients exhibit phenotypes of common human diseases, including obesity and increased incidence of hypertension and diabetes. Five of the eight known BBS genes encode basal body or cilia proteins in mice or humans, and homologues of two of the remaining genes are present in basal bodies/cilia of model organisms. Here we briefly describe the biology of cilia and flagella, we outline how studies on model organisms have led to our current understanding of the roles of these organelles and their proteins in health and disease, and we highlight the notion that the primary cilia present on cells throughout the body, even those on brain neurons, may be essential for as yet undiscovered cilium-generated signaling functions.

show abstract

Role of cilia in normal pancreas function and in diseased states

Diiorio

Rittenhouse

Bortell

et al. 2014

Birth Defects Research Pt C

View full text Add to dashboard Cite

Primary cilia play an essential role in modulating signaling cascades that shape cellular responses to environmental cues to maintain proper tissue development. Mutations in primary cilium proteins have been linked to several rare developmental disorders, collectively known as ciliopathies. Together with other disorders associated with dysfunctional cilia/centrosomes, affected individuals have increased risk of developing metabolic syndrome, neurologic disorders, and diabetes. In pancreatic tissues, cilia are found exclusively in islet and ductal cells where they play an essential role in pancreatic tissue organization. Their absence or disorganization leads to pancreatic duct abnormalities, acinar cell loss, polarity defects, and dysregulated insulin secretion. Cilia in pancreatic tissues are hubs for cellular signaling. Many signaling components, such as Hh, Notch, and Wnt, localize to pancreatic primary cilia and are necessary for proper development of pancreatic epithelium and β-cell morphogenesis. Receptors for neuroendocrine hormones, such as Somatostatin Receptor 3, also localize to the cilium and may play a more direct role in controlling insulin secretion due to somatostatin's inhibitory function. Finally, unique calcium signaling, which is at the heart of β-cell function, also occurs in primary cilia. Whereas voltage-gated calcium channels trigger insulin secretion and serve a variety of homeostatic functions in β-cells, transient receptor potential channels regulate calcium levels within the cilium that may serve as a feedback mechanism, regulating insulin secretion. This review article summarizes our current understanding of the role of primary cilia in normal pancreas function and in the diseased state.

show abstract

Nephrocystin interacts with Pyk2, p130 ^Cas , and tensin and triggers phosphorylation of Pyk2

Cited by 108 publications

References 26 publications

Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination

Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination

Cilium-generated signaling and cilia-related disorders

Role of cilia in normal pancreas function and in diseased states

Contact Info

Product

Resources

About

Nephrocystin interacts with Pyk2, p130 Cas , and tensin and triggers phosphorylation of Pyk2

Cited by 108 publications

References 26 publications

Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination

Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination

Cilium-generated signaling and cilia-related disorders

Role of cilia in normal pancreas function and in diseased states

Contact Info

Product

Resources

About

Nephrocystin interacts with Pyk2, p130 ^Cas , and tensin and triggers phosphorylation of Pyk2