“ADPKD-omics”: determinants of cyclic AMP levels in renal epithelial cells

Mehta, Yash; Lewis, Spencer A.; Leo, Kirby T.; Chen, Lihe; Park, Eui‐Jung; Raghuram, Viswanathan; Chou, Chung‐Lin; Yang, Chin‐Rang; Kikuchi, Hiroaki; Khundmiri, Syed Jalal; Poll, Brian G.; Knepper, Mark A.

doi:10.1016/j.kint.2021.10.014

Cited by 7 publications

(6 citation statements)

References 107 publications

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“…Curation, of these datasets generated a comprehensive list of 1004 unique and previously verified protein-coding ciliary genes collectively referred to here as the ciliome ( Table S1 ; ). Despite some overlap, our curated ciliome was distinct from the recently published transcriptome of motile cilia ( Patir et al, 2020 ) and primary cilia proteomes from mouse IMCD3 cells ( Ishikawa et al, 2012 ; May et al, 2021 ; Mehta et al, 2022 ; Mick et al, 2015 ) ( Table S1 ). We examined tissues from organ systems severely affected in ciliopathies, including the developing face, brain and limbs.…”

Section: Resultsmentioning

confidence: 77%

Identification of a heterogeneous and dynamic ciliome during embryonic development and cell differentiation

et al. 2023

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Primary cilia are nearly ubiquitous organelles that transduce molecular and mechanical signals. While the basic structure of the cilium and the cadre of genes that contribute to ciliary formation and function (the ciliome) are believed to be evolutionarily conserved, the presentation of ciliopathies with narrow, tissue-specific phenotypes and distinct molecular readouts suggests an unappreciated heterogeneity exists within this organelle. Here, we provide a searchable transcriptomic resource for a curated primary ciliome detailing various subgroups of differentially expressed genes within the ciliome that display tissue and temporal specificity (https://research.cchmc.org/Ciliome_Gene_Expression/). Genes within the differentially expressed ciliome exhibited a lower level of functional constraint across species suggesting organism and cell-specific function adaptation. The biological relevance of ciliary heterogeneity was functionally validated by utilizing Cas9 gene-editing to disrupt ciliary genes that displayed dynamic gene expression profiles during osteogenic differentiation of multipotent neural crest cells. Collectively, this novel primary cilia-focused resource will allow researchers to explore long-standing questions related to how tissue and cell-type specific functions and ciliary heterogeneity may contribute to the range of phenotypes associated with ciliopathies.

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Section: Resultsmentioning

confidence: 77%

Identification of a heterogeneous and dynamic ciliome during embryonic development and cell differentiation

et al. 2023

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“…Both AC5 (Wang et al, 2018) and AC6 (Rees et al, 2014) deletion individually reduces renal cyclic AMP and cyst growth in an orthologous mouse model of polycystic kidney disease, suggesting their role in ADPKD. A recent omics-level study of cAMP signaling components in kidney tissue showed that AC6 and AC5 are predominantly present in collecting ducts and less strong in proximal tubules (Mehta et al, 2022). AC5/6 are cilia localized.…”

Section: Adenylyl Cyclasesmentioning

confidence: 99%

Molecular mechanisms underlying polycystic kidney disease: From the smallest bricks to the big scenario

2024

Frontiers Research Topics

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Frontiers is more than just an open access publisher of scholarly articles: it is a pioneering approach to the world of academia, radically improving the way scholarly research is managed. The grand vision of Frontiers is a world where all people have an equal opportunity to seek, share and generate knowledge. Frontiers provides immediate and permanent online open access to all its publications, but this alone is not enough to realize our grand goals. Frontiers journal seriesThe Frontiers journal series is a multi-tier and interdisciplinary set of openaccess, online journals, promising a paradigm shift from the current review, selection and dissemination processes in academic publishing. All Frontiers journals are driven by researchers for researchers; therefore, they constitute a service to the scholarly community. At the same time, the Frontiers journal series operates on a revolutionary invention, the tiered publishing system, initially addressing specific communities of scholars, and gradually climbing up to broader public understanding, thus serving the interests of the lay society, too. Dedication to qualityEach Frontiers article is a landmark of the highest quality, thanks to genuinely collaborative interactions between authors and review editors, who include some of the world's best academicians. Research must be certified by peers before entering a stream of knowledge that may eventually reach the public -and shape society; therefore, Frontiers only applies the most rigorous and unbiased reviews. Frontiers revolutionizes research publishing by freely delivering the most outstanding research, evaluated with no bias from both the academic and social point of view. By applying the most advanced information technologies, Frontiers is catapulting scholarly publishing into a new generation. What are Frontiers Research Topics?Frontiers Research Topics are very popular trademarks of the Frontiers journals series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area.

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“…Multiple class A rhodopsin family GPCRs that are trafficked to cilia are TULP3 cargoes. One of these GPCRs, GPR161, is known to be ciliary in the IMCD3 cells ( Mukhopadhyay et al, 2013 ) and expressed highly in the kidney CCD cells ( Mehta et al, 2022 ). However, lack of GPR161 during kidney development does not cause cystogenesis ( Hwang et al, 2019 ).…”

Section: Known Tulp3 and Ift-a Cargoes As Potential Clci And Ccdca Si...mentioning

confidence: 99%

“…Both AC5 ( Wang et al, 2018 ) and AC6 ( Rees et al, 2014 ) deletion individually reduces renal cyclic AMP and cyst growth in an orthologous mouse model of polycystic kidney disease, suggesting their role in ADPKD. A recent omics-level study of cAMP signaling components in kidney tissue showed that AC6 and AC5 are predominantly present in collecting ducts and less strong in proximal tubules ( Mehta et al, 2022 ). AC5/6 are cilia localized.…”

Section: Known Tulp3 and Ift-a Cargoes As Potential Clci And Ccdca Si...mentioning

confidence: 99%

Cilia-Localized Counterregulatory Signals as Drivers of Renal Cystogenesis

Walker

Maranto

Palicharla

et al. 2022

Front. Mol. Biosci.

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Primary cilia play counterregulatory roles in cystogenesis—they inhibit cyst formation in the normal renal tubule but promote cyst growth when the function of polycystins is impaired. Key upstream cilia-specific signals and components involved in driving cystogenesis have remained elusive. Recent studies of the tubby family protein, Tubby-like protein 3 (TULP3), have provided new insights into the cilia-localized mechanisms that determine cyst growth. TULP3 is a key adapter of the intraflagellar transport complex A (IFT-A) in the trafficking of multiple proteins specifically into the ciliary membrane. Loss of TULP3 results in the selective exclusion of its cargoes from cilia without affecting their extraciliary pools and without disrupting cilia or IFT-A complex integrity. Epistasis analyses have indicated that TULP3 inhibits cystogenesis independently of the polycystins during kidney development but promotes cystogenesis in adults when polycystins are lacking. In this review, we discuss the current model of the cilia-dependent cyst activation (CDCA) mechanism in autosomal dominant polycystic kidney disease (ADPKD) and consider the possible roles of ciliary and extraciliary polycystins in regulating CDCA. We then describe the limitations of this model in not fully accounting for how cilia single knockouts cause significant cystic changes either in the presence or absence of polycystins. Based on available data from TULP3/IFT-A-mediated differential regulation of cystogenesis in kidneys with deletion of polycystins either during development or in adulthood, we hypothesize the existence of cilia-localized components of CDCA (cCDCA) and cilia-localized cyst inhibition (CLCI) signals. We develop the criteria for cCDCA/CLCI signals and discuss potential TULP3 cargoes as possible cilia-localized components that determine cystogenesis in kidneys during development and in adult mice.

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“ADPKD-omics”: determinants of cyclic AMP levels in renal epithelial cells

Cited by 7 publications

References 107 publications

Identification of a heterogeneous and dynamic ciliome during embryonic development and cell differentiation

Identification of a heterogeneous and dynamic ciliome during embryonic development and cell differentiation

Molecular mechanisms underlying polycystic kidney disease: From the smallest bricks to the big scenario

Cilia-Localized Counterregulatory Signals as Drivers of Renal Cystogenesis

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