Deficiency of β-Arrestin 2 in Dendritic Cells Contributes to Autoimmune Diseases

Cai, Yingying; Yang, Cuixia; Yu, Xiaobin; Qian, Jie; Dai, Min; Wang, Yan; Chen, Qin; Lai, Weiming; Chen, Shuai; Wang, Tingting; Zhou, Jinfeng; Ma, Ningjia; Zhang, Yue; Zhang, Ru; Shen, Nan; Xie, Xin; Du, Changsheng

doi:10.4049/jimmunol.1800261

Cited by 8 publications

(5 citation statements)

References 73 publications

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“…Cell culture experiments showed that downregulation of β-arrestin2 led to an impaired internalization of CXCR4 after CXCL12 stimulation, and it was hypothesized that this would lead to an increased migration toward high CXCL12 levels in skin. Another study found that, β-arrestin2 deficiency in dendritic cells promotes migration and cytokine production which contributes to autoimmune encephalomyelitis ( Cai et al, 2019 ). The dysregulated expression of β-arrestin1 was found to be important in context of maternal-fetal tolerance in human pregnancies ( Liu et al, 2021 ) where a strongly reduced mRNA expression of β-arrestin1 was found in villous samples of missed abortion.…”

Section: Pathophysiological Effects Of Dysregulated Grk Expression Changesmentioning

confidence: 99%

Differential Regulation of GPCRs—Are GRK Expression Levels the Key?

Matthees

Haider

Hoffmann

et al. 2021

Front. Cell Dev. Biol.

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G protein-coupled receptors (GPCRs) comprise the largest family of transmembrane receptors and their signal transduction is tightly regulated by GPCR kinases (GRKs) and β-arrestins. In this review, we discuss novel aspects of the regulatory GRK/β-arrestin system. Therefore, we briefly revise the origin of the “barcode” hypothesis for GPCR/β-arrestin interactions, which states that β-arrestins recognize different receptor phosphorylation states to induce specific functions. We emphasize two important parameters which may influence resulting GPCR phosphorylation patterns: (A) direct GPCR–GRK interactions and (B) tissue-specific expression and availability of GRKs and β-arrestins. In most studies that focus on the molecular mechanisms of GPCR regulation, these expression profiles are underappreciated. Hence we analyzed expression data for GRKs and β-arrestins in 61 tissues annotated in the Human Protein Atlas. We present our analysis in the context of pathophysiological dysregulation of the GPCR/GRK/β-arrestin system. This tissue-specific point of view might be the key to unraveling the individual impact of different GRK isoforms on GPCR regulation.

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Section: Pathophysiological Effects Of Dysregulated Grk Expression Changesmentioning

confidence: 99%

Differential Regulation of GPCRs—Are GRK Expression Levels the Key?

Matthees

Haider

Hoffmann

et al. 2021

Front. Cell Dev. Biol.

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“…Functionally, β-arrestin 2 deficiency in DC resulted in enhanced steady-state migration to SLO and aggravated disease status in various autoimmune models. 293 On a molecular level, β-arrestins, like GRKs seem to act beyond receptor desensitization leading to more complex phenotypes that cannot be explained by alterations in migratory behavior alone.…”

Section: Orientation In the Tissue: Is It All About Ccr7 Functionality?mentioning

confidence: 99%

Concepts of GPCR‐controlled navigation in the immune system

Lämmermann

Kastenmüller

2019

Immunological Reviews

113

110

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Summary G‐protein–coupled receptor ( GPCR ) signaling is essential for the spatiotemporal control of leukocyte dynamics during immune responses. For efficient navigation through mammalian tissues, most leukocyte types express more than one GPCR on their surface and sense a wide range of chemokines and chemoattractants, leading to basic forms of leukocyte movement (chemokinesis, haptokinesis, chemotaxis, haptotaxis, and chemorepulsion). How leukocytes integrate multiple GPCR signals and make directional decisions in lymphoid and inflamed tissues is still subject of intense research. Many of our concepts on GPCR ‐controlled leukocyte navigation in the presence of multiple GPCR signals derive from in vitro chemotaxis studies and lower vertebrates. In this review, we refer to these concepts and critically contemplate their relevance for the directional movement of several leukocyte subsets (neutrophils, T cells, and dendritic cells) in the complexity of mouse tissues. We discuss how leukocyte navigation can be regulated at the level of only a single GPCR (surface expression, competitive antagonism, oligomerization, homologous desensitization, and receptor internalization) or multiple GPCR s (synergy, hierarchical and non‐hierarchical competition, sequential signaling, heterologous desensitization, and agonist scavenging). In particular, we will highlight recent advances in understanding GPCR ‐controlled leukocyte navigation by intravital microscopy of immune cells in mice.

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“…During chemotaxis, chemotactic signals, such as those from PAR-2 stimulation, promote the local formation of free actin barbed ends, membrane protrusions, and leading-edge formation by interacting with cofilin and phosphatases or directly binding to LIM kinase to antagonize its ability to phosphorylate and inactivate cofilin ( 54 , 60 ). β-arrestin2 has also been shown to negatively regulate the migration of dendritic cells and play a role in inflammatory diseases ( 61 ).…”

Section: Interactions Of β-Arrestin Proteins and The Cytoskeletonmentioning

confidence: 99%

Interactions between β-arrestin proteins and the cytoskeletal system, and their relevance to neurodegenerative disorders

Szénási

Turu²,

Hunyady³

2023

Front. Endocrinol.

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β-arrestins, which have multiple cellular functions, were initially described as proteins that desensitize rhodopsin and other G protein-coupled receptors. The cytoskeletal system plays a role in various cellular processes, including intracellular transport, cell division, organization of organelles, and cell cycle. The interactome of β-arrestins includes the major proteins of the three main cytoskeletal systems: tubulins for microtubules, actins for the actin filaments, and vimentin for intermediate filaments. β-arrestins bind to microtubules and regulate their activity by recruiting signaling proteins and interacting with assembly proteins that regulate the actin cytoskeleton and the intermediate filaments. Altered regulation of the cytoskeletal system plays an essential role in the development of Alzheimer’s, Parkinson’s and other neurodegenerative diseases. Thus, β-arrestins, which interact with the cytoskeleton, were implicated in the pathogenesis progression of these diseases and are potential targets for the treatment of neurodegenerative disorders in the future.

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Deficiency of β-Arrestin 2 in Dendritic Cells Contributes to Autoimmune Diseases

Cited by 8 publications

References 73 publications

Differential Regulation of GPCRs—Are GRK Expression Levels the Key?

Differential Regulation of GPCRs—Are GRK Expression Levels the Key?

Concepts of GPCR‐controlled navigation in the immune system

Interactions between β-arrestin proteins and the cytoskeletal system, and their relevance to neurodegenerative disorders

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