<i>C</i>‐mannosylation regulates stabilization of <scp>RAMP1</scp> protein and <scp>RAMP1</scp>‐mediated cell migration

Mizuta, Hayato; Takakusaki, Ayane; Suzuki, Takehiro; Otake, Keisuke; Dohmae, Naoshi; Simizu, Siro

doi:10.1111/febs.16592

Cited by 3 publications

(3 citation statements)

References 45 publications

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“…In some C ‐mannosylated proteins, C ‐mannosylation enhances protein stability [ 11 , 12 , 13 ]. CHX chase assay revealed that C ‐mannosylated RAMP1 is more stabilized than non‐ C ‐mannosylated RAMP1 [ 13 ]. Several reports have suggested that C ‐mannosylation affects protein conformations.…”

Section: Discussionmentioning

confidence: 99%

“…In some C-mannosylated proteins, C-mannosylation enhances protein stability [11][12][13]. CHX chase assay revealed that Cmannosylated RAMP1 is more stabilized than non-Cmannosylated RAMP1 [13]. Several reports have suggested that C-mannosylation affects protein conformations.…”

Section: Discussionmentioning

confidence: 99%

“…In RNase 2, the most abundant of the 1 C 4 conformation is exist among the C‐linked mannopyranosyl residue, and this conformation is predicted to stabilize protein folding through a network of hydrogen bonds [ 12 ]. Similarly, C ‐mannosylation has been shown to enhance protein stability in RAMP1 [ 13 ]. Among reported C ‐mannosylated proteins, UNC‐5 is the most well‐studied about the relationship between C ‐mannosylation and protein stability.…”

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Destabilization of vitelline membrane outer layer protein 1 homolog (VMO1) by C‐mannosylation

et al. 2023

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C‐mannosylation is a rare type of protein glycosylation whereby a single mannose is added to the first tryptophan in the consensus sequence Trp‐Xaa‐Xaa‐Trp/Cys (in which Xaa represents any amino acid). Its consensus sequence is mainly found in proteins containing a thrombospondin type‐1 repeat (TSR1) domain and in type I cytokine receptors. In these proteins, C‐mannosylation affects protein secretion, intracellular localization, and protein stability; however, the role of C‐mannosylation in proteins that are not type I cytokine receptors and/or do not contain a TSR1 domain is less well explored. In this study, we focused on human vitelline membrane outer layer protein 1 homolog (VMO1). VMO1, which possesses two putative C‐mannosylation sites, is a 21‐kDa secreted protein that does not contain a TSR1 domain and is not a type I cytokine receptor. Mass spectrometry analyses revealed that VMO1 is C‐mannosylated at Trp105 but not at Trp44. Although C‐mannosylation does not affect the extracellular secretion of VMO1, it destabilizes the intracellular VMO1. In addition, a structural comparison between VMO1 and C‐mannosylated VMO1 showed that the modification of the mannose changes the conformation of three loops in VMO1. Taken together, our results demonstrate the first example of C‐mannosylation for protein destabilization of VMO1.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Destabilization of vitelline membrane outer layer protein 1 homolog (VMO1) by C‐mannosylation

et al. 2023

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Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins

et al. 2022

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G protein-coupled receptors (GPCRs) are known to interact with several other classes of integral membrane proteins that modulate their biology and pharmacology. However, the extent of these interactions and the mechanisms of their effects are not well understood. For example, one class of GPCR-interacting proteins, receptor activity-modifying proteins (RAMPs), comprise three related and ubiquitously expressed single-transmembrane span proteins. The RAMP family was discovered more than two decades ago, and since then GPCR–RAMP interactions and their functional consequences on receptor trafficking and ligand selectivity have been documented for several secretin (class B) GPCRs, most notably the calcitonin receptor-like receptor. Recent bioinformatics and multiplexed experimental studies suggest that GPCR–RAMP interactions might be much more widespread than previously anticipated. Recently, cryo-electron microscopy has provided high-resolution structures of GPCR–RAMP–ligand complexes, and drugs have been developed that target GPCR–RAMP complexes. In this review, we provide a summary of recent advances in techniques that allow the discovery of GPCR–RAMP interactions and their functional consequences and highlight prospects for future advances. We also provide an up-to-date list of reported GPCR–RAMP interactions based on a review of the current literature. Significance Statement Receptor activity-modifying proteins (RAMPs) have emerged as modulators of many aspects of G protein-coupled receptor (GPCR)biology and pharmacology. The application of new methodologies to study membrane protein–protein interactions suggests that RAMPs interact with many more GPCRs than had been previously known. These findings, especially when combined with structural studies of membrane protein complexes, have significant implications for advancing GPCR-targeted drug discovery and the understanding of GPCR pharmacology, biology, and regulation.

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Identification of crosstalk genes and immune characteristics between Alzheimer’s disease and atherosclerosis

An,

Zhou,

Qiu

et al. 2024

Front. Immunol.

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BackgroundAdvancements in modern medicine have extended human lifespan, but they have also led to an increase in age-related diseases such as Alzheimer’s disease (AD) and atherosclerosis (AS). Growing research evidence indicates a close connection between these two conditions.MethodsWe downloaded four gene expression datasets related to AD and AS from the Gene Expression Omnibus (GEO) database (GSE33000, GSE100927, GSE44770, and GSE43292) and performed differential gene expression (DEGs) analysis using the R package “limma”. Through Weighted gene correlation network analysis (WGCNA), we selected the gene modules most relevant to the diseases and intersected them with the DEGs to identify crosstalk genes (CGs) between AD and AS. Subsequently, we conducted functional enrichment analysis of the CGs using DAVID. To screen for potential diagnostic genes, we applied the least absolute shrinkage and selection operator (LASSO) regression and constructed a logistic regression model for disease prediction. We established a protein-protein interaction (PPI) network using STRING (https://cn.string-db.org/) and Cytoscape and analyzed immune cell infiltration using the CIBERSORT algorithm. Additionally, NetworkAnalyst (http://www.networkanalyst.ca) was utilized for gene regulation and interaction analysis, and consensus clustering was employed to determine disease subtypes. All statistical analyses and visualizations were performed using various R packages, with a significance level set at p<0.05.ResultsThrough intersection analysis of disease-associated gene modules identified by DEGs and WGCNA, we identified a total of 31 CGs co-existing between AD and AS, with their biological functions primarily associated with immune pathways. LASSO analysis helped us identify three genes (C1QA, MT1M, and RAMP1) as optimal diagnostic CGs for AD and AS. Based on this, we constructed predictive models for both diseases, whose accuracy was validated by external databases. By establishing a PPI network and employing four topological algorithms, we identified four hub genes (C1QB, CSF1R, TYROBP, and FCER1G) within the CGs, closely related to immune cell infiltration. NetworkAnalyst further revealed the regulatory networks of these hub genes. Finally, defining C1 and C2 subtypes for AD and AS respectively based on the expression profiles of CGs, we found the C2 subtype exhibited immune overactivation.ConclusionThis study utilized gene expression matrices and various algorithms to explore the potential links between AD and AS. The identification of CGs revealed interactions between these two diseases, with immune and inflammatory imbalances playing crucial roles in their onset and progression. We hope these findings will provide valuable insights for future research on AD and AS.

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C‐mannosylation regulates stabilization of RAMP1 protein and RAMP1‐mediated cell migration

Cited by 3 publications

References 45 publications

Destabilization of vitelline membrane outer layer protein 1 homolog (VMO1) by C‐mannosylation

Destabilization of vitelline membrane outer layer protein 1 homolog (VMO1) by C‐mannosylation

Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins

Identification of crosstalk genes and immune characteristics between Alzheimer’s disease and atherosclerosis

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