PKD1L1

更新于：2025-05-07

基本信息

别名

PC1-like 1 protein、PKD1L1、Polycystic kidney disease protein 1-like 1

+ [3]

简介

Component of a calcium-permeant ion channel formed by PKD1L2 and PKD1L1 in primary cilia, where it controls cilium calcium concentration, without affecting cytoplasmic calcium concentration, and regulates sonic hedgehog/SHH signaling and GLI2 transcription (PubMed:24336289). The PKD1L1:PKD2L1 channel complex is mechanosensitive only at high pressures and is highly temperature sensitive (PubMed:24336289). Also involved in left/right axis specification downstream of nodal flow by forming a complex with PKD2 in cilia to facilitate flow detection in left/right patterning (By similarity). May function as a G-protein-coupled receptor (PubMed:15203210).

关联

100 项与 PKD1L1 相关的临床结果

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100 项与 PKD1L1 相关的转化医学

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0 项与 PKD1L1 相关的专利（医药）

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项与 PKD1L1 相关的文献（医药）

2025-06-01·Journal of Environmental Sciences

Gene expression profiles of Chinese medaka (Oryzias sinensis) primary hepatocytes in response to estrone (E1), 17β-estradiol (E2) and estriol (E3)

Article

作者: Lv, Junhui ; Huai, Narma ; Zhou, Ying ; Zhu, Hua ; Zhang, Kailun ; Wang, Yue ; Li, Xiqing ; Reze, Yilihamu ; Xie, Zhongtang ; Zhang, Zhaobin

The natural estrogens, including estrone (E₁), 17β-estradiol (E₂), and estriol (E₃), are frequently detected in aquatic environment at relatively high levels. The most commonly used biomarkers for estrogens are mainly expressed in the liver of fish. Analyses of the global gene profiling in fish liver cells under estrogens treatment will provide precise toxicogenomic information of the natural estrogens which is still not well known. In this study, we developed methods for isolation and culture of primary hepatocytes from liver tissue of male Chinese medaka (Oryzias sinensis), and analyzed the global gene expression profiling in the primary hepatocytes treated with E₁ (1, 10, and 100 nmol/L), E₂ (0.01, 0.1, 1, 10, and 100 nmol/L), and E₃ (1, 10, and 100 nmol/L) using RNA-seq. It was found that 175, 248, and 218 genes were differentially expressed in the E₁, E₂, and E₃ groups, respectively. These differentially expressed genes (DEGs) were mainly enriched in Gene Ontology (GO) terms of "response to estradiol", "response to estrogen", and "lipid transport". Of the DEGs, vitellogenin genes, including vtg1, vtg2, and vtg3, were the mostly up-regulated and followed by zona pellucida genes which include zp2.3, zp2l1 and zp3a.2. In addition, genes of slc41a1, zp2.1, esr1, pkd1l1, fam20ca, best3, etc. were also obviously up-regulated by the estrogens in concentration-dependent patterns. RT-qPCR was used to validate the results of RNA-seq and found that vtg2 should be the best biomarker gene for estrogen study, which could well response to natural estrogens and weak estrogenic chemical, propyl 4-hydroxybenzoate.

2025-02-01·The American Journal of Human Genetics

CIROZ is dispensable in ancestral vertebrates but essential for left-right patterning in humans

Article

作者: Xuan Goh, Wei ; Alkelai, Anna ; Amiel, Jeanne ; Alshamsi, Aisha M ; Brady, Angela F ; Khatoo, Muznah ; Beetz, Christian ; Alkuraya, Fowzan S ; Gordon, Christopher T ; Almontashiri, Naif A M ; Alghamdi, Malak Ali ; Saad, Chadi ; Beckers, Anja ; Tan, Wen-Hann ; Bauer, Peter ; Pak, Beatrice ; Alharby, Essa ; Schweickert, Axel ; Alswaid, Abdulrahman Faiz ; Reversade, Bruno ; Yusof, Amirah ; Alfadhel, Majid ; Blum, Martin ; Vick, Philipp ; Ellard, Sian ; Dasouki, Majed ; Wakeling, Matthew ; Tripolszki, Kornelia ; Giordano, Jessica L ; Moreau de Bellaing, Anne ; Eisenhaber, Birgit ; Schafer-Kosulya, Anna ; Wapner, Ronald J ; Bertoli-Avella, Aida ; Vogel, Sebastian ; Bogusch, Susanne ; Sanlaville, Damien ; Chopra, Maya ; Maddirevula, Sateesh ; Djaziri, Nabila ; Bouvagnet, Patrice ; Stals, Karen ; Ewans, Lisa J ; Mbarek, Hamdi ; Romo, Lindsay ; Szenker-Ravi, Emmanuelle ; Gossler, Achim ; Eisenhaber, Frank ; Ott, Tim

Four genes-DAND5, PKD1L1, MMP21, and CIROP-form a genetic module that has specifically evolved in vertebrate species that harbor motile cilia in their left-right organizer (LRO). We find here that CIROZ (previously known as C1orf127) is also specifically expressed in the LRO of mice, frogs, and fish, where it encodes a protein with a signal peptide followed by 3 zona pellucida N domains, consistent with extracellular localization. We report 16 individuals from 10 families with bi-allelic CIROZ inactivation variants, which cause heterotaxy with congenital heart defects. While the knockout of Ciroz in mice also leads to situs anomalies, we unexpectedly find that its targeted inactivation in zebrafish and Xenopus does not lead to observable LR anomalies. Moreover, CIROZ is absent or obsolete in select animals with motile cilia at their LRO, including Carnivora, Atherinomorpha fish, or jawless vertebrates. In summary, this evo-devo study identifies CIROZ as an essential gene for breaking bilateral embryonic symmetry in humans and mice, whereas we witness its contemporary pseudogenization in discrete vertebrate species.

2024-07-01·Journal of Hepatology

Pkd1l1-deficiency drives biliary atresia through ciliary dysfunction in biliary epithelial cells

Article

作者: Zhu, Hao ; Lim, Yi Zou ; Kelley, Shannon ; Oertling, Estelle ; Wang, Yunguan ; Sharma, Tripti ; Zhu, Min ; Corbitt, Natasha

BACKGROUND & AIMSSyndromic biliary atresia is a cholangiopathy characterized by fibro-obliterative changes in the extrahepatic bile duct (EHBD) and congenital malformations including laterality defects. The etiology remains elusive and faithful animal models are lacking. Genetic syndromes provide important clues regarding the pathogenic mechanisms underlying the disease. We investigated the role of the gene Pkd1l1 in the pathophysiology of syndromic biliary atresia.METHODSConstitutive and conditional Pkd1l1 knockout mice were generated to explore genetic pathology as a cause of syndromic biliary atresia. We investigated congenital malformations, EHBD and liver pathology, EHBD gene expression, and biliary epithelial cell turnover. Biliary drainage was functionally assessed with cholangiography. Histology and serum chemistries were assessed after DDC (3,5-diethoxycarbony l-1,4-dihydrocollidine) diet treatment and inhibition of the ciliary signaling effector GLI1.RESULTSPkd1l1-deficient mice exhibited congenital anomalies including malrotation and heterotaxy. Pkd1l1-deficient EHBDs were hypertrophic and fibrotic. Pkd1l1-deficient EHBDs were patent but displayed delayed biliary drainage. Pkd1l1-deficient livers exhibited ductular reaction and periportal fibrosis. After DDC treatment, Pkd1l1-deficient mice exhibited EHBD obstruction and advanced liver fibrosis. Pkd1l1-deficient mice had increased expression of fibrosis and extracellular matrix remodeling genes (Tgfα, Cdkn1a, Hb-egf, Fgfr3, Pdgfc, Mmp12, and Mmp15) and decreased expression of genes mediating ciliary signaling (Gli1, Gli2, Ptch1, and Ptch2). Primary cilia were reduced on biliary epithelial cells and altered expression of ciliogenesis genes occurred in Pkd1l1-deficient mice. Small molecule inhibition of the ciliary signaling effector GLI1 with Gant61 recapitulated Pkd1l1-deficiency.CONCLUSIONSPkd1l1 loss causes both laterality defects and fibro-proliferative EHBD transformation through disrupted ciliary signaling, phenocopying syndromic biliary atresia. Pkd1l1-deficient mice function as an authentic genetic model for study of the pathogenesis of biliary atresia.IMPACT AND IMPLICATIONSThe syndromic form of biliary atresia is characterized by fibro-obliteration of extrahepatic bile ducts and is often accompanied by laterality defects. The etiology is unknown, but Pkd1l1 was identified as a potential genetic candidate for syndromic biliary atresia. We found that loss of the ciliary gene Pkd1l1 contributes to hepatobiliary pathology in biliary atresia, exhibited by bile duct hypertrophy, reduced biliary drainage, and liver fibrosis in Pkd1l1-deficient mice. Pkd1l1-deficient mice serve as a genetic model of biliary atresia and reveal ciliopathy as an etiology of biliary atresia. This model will help scientists uncover new therapeutic approaches for patients with biliary atresia, while pediatric hepatologists should validate the diagnostic utility of PKD1L1 variants.

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