APPLs: More than just adiponectin receptor binding proteins

Liu, Zhuoying; Xiao, Ting; Peng, Xiaoyan; Li, Guangdi; Hu, Fang

doi:10.1016/j.cellsig.2017.01.018

Cited by 43 publications

(32 citation statements)

References 76 publications

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“…For our set of 79 LRGs, we could identify SNPs for three LRGs of the chow network and for 17 LRGs of the HFD network (Table S4, SI). Among the genes most prominently associated with SNPs were Appl2 (Figure 4I), which mediates insulin signaling, endosomal trafficking, adiponectin and other signaling pathways [20] and Cobll1 (Figure 4J), which was strongly associated with several obesity and type 2 diabetes related markers [21, 22]. We further found the differentially expressed LRG Inhbe , a hepatokine which was recently linked to insulin resistance in human livers [23].…”

Section: Resultsmentioning

confidence: 82%

Correlation guided Network Integration (CoNI) reveals novel genetic regulators of hepatic metabolism

Vs¹,

Kuhn

et al. 2020

Preprint

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ABSTRACTThe steadily increasing amount of newly generated omics data of various types from genomics to metabolomics is a chance and a challenge to systems biology. To fully use its potential, one key is the meaningful integration of different types of omics. We here present a fully unsupervised and versatile correlation-based method, termed Correlation guided Network Integration (CoNI), to integrate multi-omics data into a hypergraph structure that allows for identification of effective regulators. Our approach further unravels single transcripts mapped to specific densely connected metabolic sub-graphs or pathways. By applying our method on transcriptomics and metabolomics data from murine livers under standard chow or high-fat-diet, we isolated eleven genes with a regulatory effect on hepatic metabolism. Subsequent in vitro and ex vivo experiments in human liver cells and human obtained liver biopsies validated seven candidates including INHBE and COBLL1, to alter lipid metabolism and to correlate with diabetes related traits such as overweight, hepatic fat content and insulin resistance (HOMA-IR). Last, we successfully applied our methods to an independent data-set to confirm its versatile and transferable character.

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Section: Resultsmentioning

confidence: 82%

Correlation guided Network Integration (CoNI) reveals novel genetic regulators of hepatic metabolism

Vs¹,

Kuhn

et al. 2020

Preprint

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“…APPL1 is so far the only known protein present on the VEEs, suggesting a functional role of this adaptor protein within this compartment (Jean-Alphonse et al 2014. APPL1 is an adaptor protein, which lacks catalytic activity but is composed by various protein and membrane interacting domains (Liu et al 2017b). It is known to represent an intermediate early endosomal compartment, positive for RAB5, prior to conversion to EEA1 endosomes (Zoncu et al 2009).…”

Section: The Very Early Endosome: a Sorting And Signalling Station Fomentioning

confidence: 99%

Driving gonadotrophin hormone receptor signalling: the role of membrane trafficking

Sposini

Hanyaloglu

2018

Reproduction

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Our understanding of G protein-coupled receptor (GPCR) signalling has significantly evolved over the past decade, whereby signalling not only occurs from the plasma membrane but continues, or is reactivated, following internalisation in to endosomal compartments. The spatial organisation of GPCRs is thus essential to decode dynamic and complex signals and to activate specific downstream pathways that elicit the appropriate cellular response. For the gonadotrophin hormone receptors, membrane trafficking has been demonstrated to play a significant role in regulating its signal activity that in turn would impact at physiological and even pathophysiological level. Here, we will describe the developments in our understanding of the role of 'location' in gonadotrophin hormone receptor signalling, and how these receptors have unveiled fundamental mechanisms of signal regulation likely to be pertinent for other GPCRs. We will also discuss the potential impact of spatially controlled gonadotrophin hormone receptor signalling in both health and disease, and the therapeutic possibilities this new understanding of these receptors, so key in reproduction, offers.Reproduction (2018) 156 R195-R208 R196 Reproduction (2018) 156 R195-R208 https://rep.bioscientifica.com Gonadotrophin hormone receptor trafficking R197 https://rep.bioscientifica.com Reproduction (2018) 156 R195-R208 S Sposini and A C Hanyaloglu R198 Reproduction (2018) 156 R195-R208 https://rep.bioscientifica.com S Sposini and A C Hanyaloglu R200 Reproduction (2018) 156 R195-R208 https://rep.bioscientifica.com S Sposini and A C Hanyaloglu R202 Reproduction (2018) 156 R195-R208 https://rep.bioscientifica.com S Sposini and A C Hanyaloglu R204 Reproduction (2018) 156 R195-R208 References Abbe E. 1873 Beitrage zur Theorie des Mikroskops und der mikroskopischen Wahrnehmung. Archiv für mikroskopische Anatomie 9 413-420. (https:// doi.org/10.1007/BF02956173) Aittomaki K, Lucena JL, Pakarinen P, Sistonen P, Tapanainen J, Gromoll J, Kaskikari R, Sankila EM, Lehvaslaiho H, Engel AR et al. 1995 Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell 82 959-968. (https://doi. org/10.1016/0092-8674(95)90275-9) Andric N & Ascoli M 2006 A delayed gonadotropin-dependent and growth factor-mediated activation of the extracellular signal-regulated kinase 1/2 cascade negatively regulates aromatase expression in granulosa cells. Molecular Endocrinology 20 3308-3320. (https://doi.org/10.1210/ me.2006-0241)

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“…Изучение адипонектинового сигналинга в миоцитах, гепатоцитах, адипоцитах и ряде других клеток показало, что по своей структурно-функциональной организации он достаточно консервативен [18]. Во всех типах клеток основными компонентами, осуществляющими сопряжение AdipoR1 и AdipoR2 с внутриклеточными эффекторами, являются адапторные белки APLL-1 и APPL-2, а также ретикулярный белок ERp46 (Endoplasmic reticulum protein 46), рецепторный белок RACK1 (Receptor for activated C Kinase 1) и протеинкиназа CK2β (Casein kinase 2β) [19,20,21,22].…”

Section: адипонектиновые рецепторы и адипонектиновый сигналингunclassified

“…Белки APLL-1 и APPL-2, несмотря на существенные различия в их функциональной активности, являются основными трансдукторными компонентами адипонектинового сигналинга. Они функционально взаимодействуют с обоими типами адипонектиновых рецепторов [20,22]. Белок APPL-1 передает адипонектиновый сигнал с активированного рецептора на нижележащие каскады, в то время как APPL-2, напротив, препятствует его передаче.…”

Section: адипонектиновые рецепторы и адипонектиновый сигналингunclassified

Adiponectin as an Endogenous Regulator of the Hypothalamic-Pituitary-Gonadal Axis

Ryzhov

Шпаков

2018

Transl. med. (Print)

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Adiponectin is the most important adipokine controlling the food behavior and energy homeostasis. At present, there is much evidence that adiponectin also regulates the functions of the reproductive system, and its targets are hypothalamic neurons responsible for the synthesis and secretion of gonadoliberin, the pituitary gonadotrophs producing the luteinizing hormone, and the gonads. In the target tissues, which are blocks of the hypothalamic-pituitary-gonadal axis, all the main components of adiponectin-regulated signaling system, including adiponectin and both types of adiponectin receptors, are detected. The impairments in the adiponectin signaling pathways lead to the development of reproductive dysfunctions, as a result of which this pathways in the future can become one of the most important targets of therapy of diseases of the male and female reproductive systems. In the review, the current state of the problem of the participation of adiponectin in the functioning of the hypothalamic-pituitary-gonadal axis, and the relationship between the functional status of the reproductive system and the activity of the adiponectin system in hypothalamic neurons, gonadotrophs and gonads are considered.

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APPLs: More than just adiponectin receptor binding proteins

Cited by 43 publications

References 76 publications

Correlation guided Network Integration (CoNI) reveals novel genetic regulators of hepatic metabolism

Correlation guided Network Integration (CoNI) reveals novel genetic regulators of hepatic metabolism

Driving gonadotrophin hormone receptor signalling: the role of membrane trafficking

Adiponectin as an Endogenous Regulator of the Hypothalamic-Pituitary-Gonadal Axis

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