Coronin-1C Protein and Caveolin Protein Provide Constitutive and Inducible Mechanisms of Rac1 Protein Trafficking

Williamson, Rosalind C.; Cowell, Christopher A. M.; Reville, Thomas; Roper, James A.; Rendall, Thomas; Bass, Mark D.

doi:10.1074/jbc.m115.640367

Cited by 14 publications

(19 citation statements)

References 36 publications

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“…Of the five genes whose behavior most strongly mirrored that of the Yellow gene cluster as a whole, two— CORO1C and C8orf83 —are less well-studied and have not been previously associated with influenza vaccine responses. CORO1C encodes the coronin-1C protein, a member of the WD repeat protein family that is involved in a variety of cellular processes, including signal transduction and gene regulation, and may be involved in fibroblast migration 80 . C8orf83 encodes TRIQK, which is a small protein highly conserved across vertebrates with largely unknown function and may have undiscovered roles in immunity 81 .…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic signatures of cellular and humoral immune responses in older adults after seasonal influenza vaccination identified by data-driven clustering

Voigt

Grill

Zimmermann

et al. 2018

Sci Rep

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PBMC transcriptomes after influenza vaccination contain valuable information about factors affecting vaccine responses. However, distilling meaningful knowledge out of these complex datasets is often difficult and requires advanced data mining algorithms. We investigated the use of the data-drivenWorldwide, influenza affects 5-10% of adults annually, and results in an estimated 250,000 to 500,000 deaths 1 . Influenza morbidity and influenza-associated deaths increase significantly with age 2,3 , and more than 90% of influenza-associated deaths occur in individuals ≥65 years of age 4 . Although seasonal influenza vaccination offers protection against severe influenza disease, levels of protection vary between seasons, individuals, and agetending to be lower in elderly populations [5][6][7][8][9][10][11][12] . In fact, the effectiveness of seasonal trivalent inactivated influenza vaccination among community-dwelling older adults has been estimated to be only 30-40% 6,[12][13][14] . With the aging of populations in the U.S. and globally, it is imperative that influenza vaccine-induced immunity in older adults be better understood [15][16][17] . Systems vaccinology and vaccinomics, the application of systems biology to the study of vaccines, are a promising method to better understand human immune responses to vaccines from a holistic perspective 18,19 . A seminal paper by Querec et al. in 2008 applied a systems biology approach to study yellow fever vaccine-induced immunity and identified novel genes involved in vaccine-induced antibody and CD8+ T cell responses whose expression levels could predict immunogenicity of the vaccine in subjects, setting a new standard for vaccine studies 20 . Such systems biology approaches provide complementary insights to reductionist approaches by revealing novel interactions between immune system processes critical to developing immune responses to vaccines 21 . Systems biology approaches have been previously applied to the study of seasonal influenza vaccination

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Section: Discussionmentioning

confidence: 99%

Transcriptomic signatures of cellular and humoral immune responses in older adults after seasonal influenza vaccination identified by data-driven clustering

Voigt

Grill

Zimmermann

et al. 2018

Sci Rep

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“…In these studies, antibodies (Ab) raised against the dimerisation domain of sdc4 exhibited a blocking effect on IL-1-induced ERK signalling, but the mechanism by which the loss or inhibition of sdc4 interfered with IL1 signalling remains unclear 6. Interestingly, recent evidence suggests that trafficking of the IL-1 receptor (IL1R1) involves the formation of caveolin vesicles8 and that sdc4 may regulate the caveolin-mediated endocytosis of signalling molecules such as Rac1,9 as well as of cell surface receptors such as integrins 10…”

Section: Introductionmentioning

confidence: 99%

Antibody-mediated inhibition of syndecan-4 dimerisation reduces interleukin (IL)-1 receptor trafficking and signalling

Godmann¹,

Bollmann

Korb-Pap³

et al. 2020

Ann Rheum Dis

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ObjectiveSyndecan-4 (sdc4) is a cell-anchored proteoglycan that consists of a transmembrane core protein and glucosaminoglycan (GAG) side chains. Binding of soluble factors to the GAG chains of sdc4 may result in the dimerisation of sdc4 and the initiation of downstream signalling cascades. However, the question of how sdc4 dimerisation and signalling affects the response of cells to inflammatory stimuli is unknown.MethodsSdc4 immunostaining was performed on rheumatoid arthritis (RA) tissue sections. Interleukin (IL)-1 induced extracellular signal-regulated kinases (ERK) phosphorylation and matrix metalloproteinase-3 production was investigated. Il-1 binding to sdc4 was investigated using immunoprecipitation. IL-1 receptor (IL1R1) staining on wild-type, sdc4 and IL1R1 knockout fibroblasts was performed in fluorescence-activated cell sorting analyses. A blocking sdc4 antibody was used to investigate sdc4 dimerisation, IL1R1 expression and the histological paw destruction in the human tumour necrosis factor-alpha transgenic mouse.ResultsWe show that in fibroblasts, the loss of sdc4 or the antibody-mediated inhibition of sdc4 dimerisation reduces the cell surface expression of the IL-1R and regulates the sensitivity of fibroblasts to IL-1. We demonstrate that IL-1 directly binds to sdc4 and in an IL-1R-independent manner leads to its dimerisation. IL-1-induced dimerisation of sdc4 regulates caveolin vesicle-mediated trafficking of the IL1R1, which in turn determines the responsiveness to IL-1. Administration of antibodies (Ab) against the dimerisation domain of sdc4, thus, strongly reduces the expression IL1R1 on arthritic fibroblasts both in vitro and an animal model of human RA.ConclusionCollectively, our data suggest that Ab that specifically inhibit sdc4 dimerisation may support anti-IL-1 strategies in diseases such as inflammatory arthritis.

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“…Previous work from others showed that Cav-1 modulates Rho GTPase signaling in non-neuronal cells (Baltierrez-Hoyos et al, 2012; Lim et al, 2014). Because Cav-1 has been shown to colocalize and modulate Rho GTPase activity in non-neuronal cells (Cheng et al, 2010; Bassi et al, 2011; Diaz et al, 2014; Williamson et al, 2015; Coelho-Santos et al, 2016; Xu et al, 2016), the present study tested whether Cav-1 was also involved in Rho GTPase-mediated axonal growth and neuronal differentiation in human neurons derived from induced pluripotent stem cells (iPSCs). A better mechanistic understanding of this interplay within neurons could yield potential targets for promoting functional neuroplasticity.…”

Section: Introductionmentioning

confidence: 99%

Caveolin-1 Phosphorylation Is Essential for Axonal Growth of Human Neurons Derived From iPSCs

Wang

Zhang

Almenar-Queralt

et al. 2019

Front. Cell. Neurosci.

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Proper axonal growth and guidance is essential for neuron differentiation and development. Abnormal neuronal development due to genetic or epigenetic influences can contribute to neurological and mental disorders such as Down syndrome, Rett syndrome, and autism. Identification of the molecular targets that promote proper neuronal growth and differentiation may restore structural and functional neuroplasticity, thus improving functional performance in neurodevelopmental disorders. Using differentiated human neuronal progenitor cells (NPCs) derived from induced pluripotent stem cells (iPSCs), the present study demonstrates that during early stage differentiation of human NPCs, neuron-targeted overexpression constitutively active Rac1 (Rac1CA) and constitutively active Cdc42 (Cdc42CA) enhance expression of P-Cav-1, T-Cav-1, and P-cofilin and increases axonal growth. Similarly, neurontargeted over-expression of Cav-1 (termed SynCav1) increases axonal development by increasing both axon length and volume. Moreover, inhibition of Cav-1(Y14A) phosphorylation blunts Rac1/Cdc42-mediated both axonal growth and differentiation of human NPCs and SynCav1(Y14A)-treated NPCs exhibited blunted axonal growth. These results suggest that: (1) SynCav1-mediated dendritic and axonal growth in human NPCs is dependent upon P-Cav-1, (2) P-Cav-1 is necessary for proper axonal growth during early stages of neuronal differentiation, and (3) Rac1/Cdc42CAmediated neuronal growth is in part dependent upon P-Cav-1. In conclusion, Cav-1 phosphorylation is essential for human neuronal axonal growth during early stages of neuronal differentiation.

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Coronin-1C Protein and Caveolin Protein Provide Constitutive and Inducible Mechanisms of Rac1 Protein Trafficking

Cited by 14 publications

References 36 publications

Transcriptomic signatures of cellular and humoral immune responses in older adults after seasonal influenza vaccination identified by data-driven clustering

Transcriptomic signatures of cellular and humoral immune responses in older adults after seasonal influenza vaccination identified by data-driven clustering

Antibody-mediated inhibition of syndecan-4 dimerisation reduces interleukin (IL)-1 receptor trafficking and signalling

Caveolin-1 Phosphorylation Is Essential for Axonal Growth of Human Neurons Derived From iPSCs

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