Polycystic kidney disease: The complete structure of the PKD1 gene and its protein

Gluecksmann-Kuis,; Tayber, Olga; Woolf, Elizabeth A.; Bougueleret, Lydie; Deng, Nanhua; Alperin, Geoffrey D; Iris, François; Hawkins, F. K. L.; Munro, Cheryl; Lakey, Nathan; Duyk, Geoffrey M.; Schneider, Michael; Geng, Lin; Zhang, F.; Zhao, Zhiyong; Torosian, Stephen Dale; Zhou, Juling; Reeders, Stephen T.; Bork, Peer; Pohlschmidt, Marita; Löhning, Corinna; Kraus, Bernhard; Nowicka, Urszula; Leung, Anna Oi Wah; Frischauf, Anna‐Maria

doi:10.1016/0092-8674(95)90339-9

Cited by 527 publications

(18 citation statements)

References 52 publications

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“…With the exception of polycystin-1 (PKD1), these proteins are members of the TRP family of ion channels (Ramsey et al, 2006). PKD1s are a family of putative 11-transmembrane–spanning domain proteins of unknown function (The International Polycystic Kidney Disease Consortium, 1995; Hughes et al, 1995; Yuasa et al, 2002). PKD1 has been proposed to be a GPCR (Parnell et al, 1998, 2002), an integral component of a channel complex via its last six transmembrane domains (Ponting et al, 1999; Hanaoka et al, 2000), and a novel receptor (Kim et al, 2016).…”

Section: Primary Cilia Ion Channelsmentioning

confidence: 99%

Progress in ciliary ion channel physiology

Pablo

DeCaen

Clapham

2016

Journal of General Physiology

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Mammalian cilia are ubiquitous appendages found on the apical surface of cells. Primary and motile cilia are distinct in both morphology and function. Most cells have a solitary primary cilium (9+0), which lacks the central microtubule doublet characteristic of motile cilia (9+2). The immotile primary cilia house unique signaling components and sequester several important transcription factors. In contrast, motile cilia commonly extend into the lumen of respiratory airways, fallopian tubes, and brain ventricles to move their contents and/or produce gradients. In this review, we focus on the composition of putative ion channels found in both types of cilia and in the periciliary membrane and discuss their proposed functions. Our discussion does not cover specialized cilia in photoreceptor or olfactory cells, which express many more ion channels.

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Section: Primary Cilia Ion Channelsmentioning

confidence: 99%

Progress in ciliary ion channel physiology

Pablo

DeCaen

Clapham

2016

Journal of General Physiology

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“…PKD1 is a large and composite gene (46 exons) that produces a 14-kb mRNA and encodes protein of over 4000 amino acids in length (7, 8, 11, 13). On the other hand, PKD-2 is smaller (15 exons) and encodes a protein less than 1000 amino acids in length (11).…”

Section: Discussionmentioning

confidence: 99%

“…It is an integral membrane protein, which is found primarily in plasma membranes but also in the primary cilium and less abundant in adult than fetal epithelia. It is overexpressed in most, but not all, cysts in kidneys from patients with ADPKD and involved in adhesive protein–protein, cell–cell, and cell–matrix interactions (7, 14). …”

Section: Discussionmentioning

confidence: 99%

A Case of New Familiar Genetic Variant of Autosomal Dominant Polycystic Kidney Disease-2: A Case Study

et al. 2015

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BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is characterized by renal cyst formation due to mutations in genes coding for polycystin-1 [PKD1 (85–90% of cases), on ch 16p13.3] and polycystin-2 [PKD2 (10–15% of cases), on ch 4q13-23] and PKD3 gene (gene unmapped). It is also associated with TSC2/PKD1 contiguous gene syndrome. ADPKD is usually inherited, but new mutations without a family history occur in approximately 10% of the cases.Case presentationA 17-year-old boy was followed up for bilateral cystic kidney disease, hypertension, and obesity since he was 13 years old. The diagnosis was an accidental finding during abdominal CT at age 13 to rule out appendicitis. A renal ultrasonogram also demonstrated a multiple bilateral cysts. Because of parental history of bilateral renal cysts, PKD1 and PKD2, genetic testing was ordered. Results showed, PKD2 variant 1:3 bp deletion of TGT; nucleotide position: 1602–1604; codon position: 512–513; mRNA reading frame maintained. The same mutation was later identified in his father.ConclusionA smaller number of patients have a defect in the PKD2 locus on chromosome 4 (resulting in PKD2 disease). There are no known published cases on this familiar genetic variant of ADPKD-2 cystic kidney disease. In this case, the disease is present unusually early in life.

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“…Recent studies have suggested that the prevalence of PKD2 mutations may be higher, between 26 and 36% [2]. The PKD1 gene product, polycystin-1, is a large 460-kDa transmembrane glycoprotein of largely unknown biochemical function [3]. It has been shown to interact with the PKD2 gene product, polycystin-2, through its C-terminal intracellular tail.…”

Section: Molecular Basis Of Diseasementioning

confidence: 99%

Therapeutic Advances in the Treatment of Polycystic Kidney Disease

Riella

Czarnecki

Steinman³

2015

Nephron Clin Pract

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The spectrum of polycystic kidney disease (PKD) comprises a family of inherited syndromes defined by renal cyst formation and growth, progressive renal function loss and variable extrarenal manifestations. The most common form, autosomal-dominant PKD is caused by mutations in one of two genes, PKD1 or PKD2. Recent developments in genomic and proteomic medicine have resulted in the discovery of novel genes implicated in the wide variety of less frequent, recessive PKD syndromes. Cysts are the disease, and overall cystic burden, measured by MRI as total kidney volume, is being established as the best available biomarker of disease progression. Current state-of-the-art therapy is aimed at quality treatment for chronic renal insufficiency and cyst-related complications. Recent therapeutic studies have focused on mechanisms reducing intracellular cyclic AMP levels, blocking the renin-angiotensin-aldosterone system and inhibiting the mTOR-signaling pathway. PKD therapies with vasopressin antagonists and somatostatin analogues result in the reduction of intracellular cAMP levels and have shown limited clinical success, but side effects are prominent. Similarly, mTOR pathway inhibition has not shown significant therapeutic benefits. While the HALT-PKD study will answer questions by the end of 2014 about the utility of renin-angiotensin-aldosterone system blockade and aggressive blood pressure control, the next generation of PKD therapy studies targeting proliferative mechanisms of cyst expansion are already under way. Advances in research on the molecular mechanisms of cystogenesis will help design novel targeted PKD therapies in the future.

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Polycystic kidney disease: The complete structure of the PKD1 gene and its protein

Cited by 527 publications

References 52 publications

Progress in ciliary ion channel physiology

Progress in ciliary ion channel physiology

A Case of New Familiar Genetic Variant of Autosomal Dominant Polycystic Kidney Disease-2: A Case Study

Therapeutic Advances in the Treatment of Polycystic Kidney Disease

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