Fatty acylated caveolin-2 is a substrate of insulin receptor tyrosine kinase for insulin receptor substrate-1-directed signaling activation

Kwon, Hayeong; Lee, Jaewoong; Jeong, Kyuho; Jang, Donghwan; Pak, Yunbae

doi:10.1016/j.bbamcr.2015.02.002

Cited by 30 publications

(18 citation statements)

References 54 publications

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“…IRS1 , a substrate of insulin receptor tyrosine kinase, have a central role in the insulin stimulated signaling and is a candidate gene of T2D 69 . We were not able to replicate the expression found in cohort 1.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic and Transcriptional Alterations in Human Adipose Tissue of Polycystic Ovary Syndrome

Kokosar

Benrick

Perfilyev

et al. 2016

Sci Rep

106

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Genetic and epigenetic factors may predispose women to polycystic ovary syndrome (PCOS), a common heritable disorder of unclear etiology. Here we investigated differences in genome-wide gene expression and DNA methylation in adipose tissue from 64 women with PCOS and 30 controls. In total, 1720 unique genes were differentially expressed (Q < 0.05). Six out of twenty selected genes with largest expression difference (CYP1B1, GPT), genes linked to PCOS (RAB5B) or type 2 diabetes (PPARG, SVEP1), and methylation (DMAP1) were replicated in a separate case-control study. In total, 63,213 sites (P < 0.05) and 440 sites (Q < 0.15) were differently methylated. Thirty differentially expressed genes had corresponding changes in 33 different DNA methylation sites. Moreover, a total number of 1913 pairs of differentially expressed “gene-CpG” probes were significantly correlated after correction for multiple testing and corresponded with 349 unique genes. In conclusion, we identified a large number of genes and pathways that are affected in adipose tissue from women with PCOS. We also identified specific DNA methylation pathways that may affect mRNA expression. Together, these novel findings show that women with PCOS have multiple transcriptional and epigenetic changes in adipose tissue that are relevant for development of the disease.

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Section: Discussionmentioning

confidence: 99%

Epigenetic and Transcriptional Alterations in Human Adipose Tissue of Polycystic Ovary Syndrome

Kokosar

Benrick

Perfilyev

et al. 2016

Sci Rep

106

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“…In myocytes, miR-29 reduces insulin sensitivity by repressing IRS-1 , a target which is also bound in adipose tissue 35 . HITS-CLIP also reveals miR-29 binding sites in Myo1c and Cav2 , two genes involved in downstream propagation of insulin signaling 36,37 , suggesting overlapping function with the insulin de-sensitizing effect of miR-29 in liver 38,39 . In heart, miR-29 suppresses fibrosis by targeting Col3a1, Fbn1 , and Eln 24 .…”

Section: Figmentioning

confidence: 98%

AGO HITS-CLIP in Adipose Tissue Reveals miR-29 as a Post-Transcriptional Regulator of Leptin

O’Connor

Murphy

et al. 2020

Preprint

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MicroRNAs (miRNAs) are short, non-coding RNAs that associate with Argonaute (AGO) to regulate mRNA stability and translation. While individual miRNAs have been shown to play important roles in white and brown adipose tissue in normal physiology and disease 1,2,3 , a comprehensive analysis of miRNA activity in these tissues has not been performed. We used high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP) to comprehensively characterize the network of high-confidence, in vivo mRNA:miRNA interactions across white and brown fat, revealing over 100,000 unique miRNA binding sites. Targets for each miRNA were ranked to generate a catalog of miRNA binding activity, and the miR-29 family emerged as a top regulator of adipose tissue gene expression. Among the top targets of miR-29 was leptin, an adipocyte-derived hormone that acts on the brain to regulate food intake and energy expenditure 4 . Two independent miR-29 binding sites in the leptin 3'-UTR were validated using luciferase assays, and miR-29 gain and loss-of-function modulated leptin mRNA and protein secretion in primary adipocytes. In mice, miR-29 abundance inversely correlated with leptin levels in two independent models of obesity. This work represents the only experimentally generated miRNA targetome in adipose tissue and identifies the first known post-transcriptional regulator of leptin. Future work aimed at manipulating miR-29:leptin binding may provide a therapeutic opportunity to treat obesity and its sequelae.Much of the work on adipocyte development and function over the last several decades has focused on transcriptional regulators. These include PPARG2, which is necessary and sufficient for the development and maintenance of white and brown adipocytes 5 , and PRDM16, which regulates brown and beige adipocyte identity 6,7 . More recently, it has become clear that post-transcriptional regulators also play 3 a key role in influencing adipocyte phenotype. Studies with adipose-specific dicer KO mice demonstrate that microRNAs (miRNAs) are essential in regulating adipogenesis, insulin sensitivity and non-shivering thermogenesis 8,9 . Several individual miRNAs have been shown to contribute to these phenotypic effects.miR-133 represses BAT function by directly targeting Prdm16 and inhibiting expression of thermogenic genes 2 . miR-196a induces browning of WAT by targeting Hoxc8 1 , and miR-26 protects mice from dietinduced obesity by blocking adipogenesis 10 . These studies, and most others in adipose tissue, rely on computational predictions and low-throughput validation to identify miRNA targets. Although highthroughput crosslinking techniques to map the miRNA targetome have been applied to liver, brain, heart and other tissues 11,12,13 , thus far, no comprehensive targetome has been described for adipose tissue.To profile the complete network of in vivo, adipose-specific miRNA binding activity across both brown and white fat, we used AGO HITS-CLIP on interscapular brown adipose tissue (iBAT) and epididymal white a...

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“…The discovery of cav-1, the first genuine marker of caveolae, has been decisive in the understanding of the biological significance of the caveolar network. Three members of the caveolin gene family, cav-1 (VIP21), cav-2, and cav-3 [ 34 ], have been identified with similar structure ( Figure 1 ) and with variable level of expression between different organs and tissues in mammals [ 35 , 36 , 37 ]. All caveolin proteins are located on the cell surface and intracellularly in the Golgi apparatus, Golgi-derived vesicles, and endoplasmic reticulum (ER).…”

Section: Origin Of Ecs and Formation Of The Vascular Threementioning

confidence: 99%

Caveolae and Lipid Rafts in Endothelium: Valuable Organelles for Multiple Functions

Filippini

D’Alessio

2020

Biomolecules

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Caveolae are flask-shaped invaginations of the plasma membrane found in numerous cell types and are particularly abundant in endothelial cells and adipocytes. The lipid composition of caveolae largely matches that of lipid rafts microdomains that are particularly enriched in cholesterol, sphingomyelin, glycosphingolipids, and saturated fatty acids. Unlike lipid rafts, whose existence remains quite elusive in living cells, caveolae can be clearly distinguished by electron microscope. Despite their similar composition and the sharing of some functions, lipid rafts appear more heterogeneous in terms of size and are more dynamic than caveolae. Following the discovery of caveolin-1, the first molecular marker as well as the unique scaffolding protein of caveolae, we have witnessed a remarkable increase in studies aimed at investigating the role of these organelles in cell functions and human disease. The goal of this review is to discuss the most recent studies related to the role of caveolae and caveolins in endothelial cells. We first recapitulate the major embryological processes leading to the formation of the vascular tree. We next discuss the contribution of caveolins and cavins to membrane biogenesis and cell response to extracellular stimuli. We also address how caveolae and caveolins control endothelial cell metabolism, a central mechanism involved in migration proliferation and angiogenesis. Finally, as regards the emergency caused by COVID-19, we propose to study the caveolar platform as a potential target to block virus entry into endothelial cells.

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Fatty acylated caveolin-2 is a substrate of insulin receptor tyrosine kinase for insulin receptor substrate-1-directed signaling activation

Cited by 30 publications

References 54 publications

Epigenetic and Transcriptional Alterations in Human Adipose Tissue of Polycystic Ovary Syndrome

Epigenetic and Transcriptional Alterations in Human Adipose Tissue of Polycystic Ovary Syndrome

AGO HITS-CLIP in Adipose Tissue Reveals miR-29 as a Post-Transcriptional Regulator of Leptin

Caveolae and Lipid Rafts in Endothelium: Valuable Organelles for Multiple Functions

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