Polycystins, calcium signaling, and human diseases

Delmas, Patrick; Padilla, Françoise; Osorio, Nancy; Coste, Bertrand; Raoux, Matthieu; Crest, Marcel

doi:10.1016/j.bbrc.2004.08.044

Cited by 102 publications

(85 citation statements)

References 48 publications

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“…Bending of the ciliary axoneme due to fluid movement has been shown to induce a Ca 2ϩ -response (Praetorius and Spring, 2001), which is dependent on PC-1 and PC-2. This calcium response is thought to be important in detecting fluid movement for maintaining tissue function, because mutations leading to its loss result in cyst development (Delmas et al, 2004;Liu et al, 2005b;Köttgen, 2007;Weimbs, 2007;Yoder, 2007). In addition, in the absence of flow PC-1 may be proteolytically processed (Chauvet et al, 2004), leading to the nuclear translocation of the transcription factor STAT6 and co-activator P100 (Low et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Characterization of primary cilia and Hedgehog signaling during development of the human pancreas and in human pancreatic duct cancer cell lines

Nielsen

Møllgård

Clément

et al. 2008

Developmental Dynamics

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Hedgehog (Hh) signaling controls pancreatic development and homeostasis; aberrant Hh signaling is associated with several pancreatic diseases. Here we investigated the link between Hh signaling and primary cilia in the human developing pancreatic ducts and in cultures of human pancreatic duct adenocarcinoma cell lines, PANC-1 and CFPAC-1. We show that the onset of Hh signaling from human embryogenesis to fetal development is associated with accumulation of Hh signaling components Smo and Gli2 in duct primary cilia and a reduction of Gli3 in the duct epithelium. Smo, Ptc, and Gli2 localized to primary cilia of PANC-1 and CFPAC-1 cells, which may maintain high levels of nonstimulated Hh pathway activity. These findings indicate that primary cilia are involved in pancreatic development and postnatal tissue homeostasis.

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Section: Introductionmentioning

confidence: 99%

Characterization of primary cilia and Hedgehog signaling during development of the human pancreas and in human pancreatic duct cancer cell lines

Nielsen

Møllgård

Clément

et al. 2008

Developmental Dynamics

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“…mal dominant polycystic kidney disease is caused by inactivating mutations of PKD1 (which produces polycystin-1 (PC1)) or PKD2 (which produces polycystin-2 (PC2)) (1). Also, mutations of Tg737, kif3a, and cpk, which encode the ciliary proteins polaris, Kif3a, and cystin, cause autosomal recessive polycystic kidney disease (6 -9).…”

mentioning

confidence: 99%

“…PC1 is a 4303-amino acid cell-surfaceexpressed protein that has a multidomain extracellular region, an 11 transmembrane region (10), and an ϳ200 amino acid cytoplasmic C-terminal tail (3), whereas PC2 is a Ca 2ϩ -permeable cation channel belonging to the transient receptor potential family (11)(12)(13). There is compelling evidence that PC1 forms heterodimers with PC2 to create a polycystin complex that localizes with Tg737, Kif3a, and Cpk in cilium and may be involved in cell-matrix interfaces and cell-cell contacts (1,5,9,14). The polycystin complex, either through its association with cilium or cell-to-cell or cell-to-matrix interactions, has been implicated as a mechano-sensor in renal epithelial cells (15)(16)(17).…”

mentioning

confidence: 99%

Cilia-like Structures and Polycystin-1 in Osteoblasts/Osteocytes and Associated Abnormalities in Skeletogenesis and Runx2 Expression

Xiao

Zhang

Mahlios

et al. 2006

Journal of Biological Chemistry

234

259

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We examined the osteoblast/osteocyte expression and function of polycystin-1 (PC1), a transmembrane protein that is a component of the polycystin-2 (PC2)-ciliary mechano-sensor complex in renal epithelial cells. We found that MC3T3-E1 osteoblasts and MLO-Y4 osteocytes express transcripts for PC1, PC2, and the ciliary proteins Tg737 and Kif3a. Immunohistochemical analysis detected cilia-like structures in MC3T3-E1 osteoblastic and MLO-Y4 osteocyte-like cell lines as well as primary osteocytes and osteoblasts from calvaria. Pkd1 m1Bei mice have inactivating missense mutations of Pkd1 gene that encode PC1. Pkd1 m1Bei homozygous mutant mice demonstrated delayed endochondral and intramembranous bone formation, whereas heterozygous Pkd1 m1Bei mutant mice had osteopenia caused by reduced osteoblastic function. Heterozygous and homozygous Pkd1 m1Bei mutant mice displayed a gene dose-dependent decrease in the expression of Runx2 and osteoblastrelated genes. In addition, overexpression of constitutively active PC1 C-terminal constructs in MC3T3-E1 osteoblasts resulted in an increase in Runx2 P1 promoter activity and endogenous Runx2 expression as well as an increase in osteoblast differentiation markers. Conversely, osteoblasts derived from Pkd1 m1Bei homozygous mutant mice had significant reductions in endogenous Runx2 expression, osteoblastic markers, and differentiation capacity ex vivo. Co-expression of constitutively active PC1 C-terminal construct into Pkd1 m1Bei homozygous osteoblasts was sufficient to normalize Runx2 P1 promoter activity. These findings are consistent with a possible functional role of cilia and PC1 in anabolic signaling in osteoblasts/osteocytes.

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“…TRPP family: The TRPP family (reviewed by Delmas et al, 2004a, Delmas, 2005Giamarchi et al, 2006;Witzgall, 2007) subsumes the polycystins that are divided into two structurally distinct groups, polycystic kidney disease 1-like (PKD1-like) and polycystic kidney disease 2-like (PKD2-like). Members of the PKD1-like group, in mammals, include PKD1 (recently reclassified as TRPP1), PDKREJ, PKD1L1, PKD1L2 and PKD1L3.…”

Section: Transient Receptor Potential (Trp) Cationmentioning

confidence: 99%