TRAPPC9: Novel insights into its trafficking and signaling pathways in health and disease (Review)

Mbimba, Thomas; Hussein, Nazar; Najeed, Ayesha; Safadi, Fayez F.

doi:10.3892/ijmm.2018.3889

Cited by 17 publications

(20 citation statements)

References 43 publications

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“…TRAPPC9, also known as NIK-and-IKK2-binding protein (NIBP), is extensively expressed in the nervous system and plays a role in regulating neurogenesis and neuronal differentiation. It plays a role in both the regulation of protein trafficking and the neuronal NF-kB signaling pathway [19,20]. In the former, TRAPPC9 is involved in the trafficking of cargo from the endoplasmic reticulum to the Golgi; interestingly, impairment of vesicular trafficking has been observed as a common biologic defect in neurologic disorders [19].…”

Section: Discussionmentioning

confidence: 99%

“…It plays a role in both the regulation of protein trafficking and the neuronal NF-kB signaling pathway [19,20]. In the former, TRAPPC9 is involved in the trafficking of cargo from the endoplasmic reticulum to the Golgi; interestingly, impairment of vesicular trafficking has been observed as a common biologic defect in neurologic disorders [19]. In addition, TRAPPC9 is involved in the activation of NFkB, which remains sequestered in the cytoplasm while is not activated [20].…”

Section: Discussionmentioning

confidence: 99%

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Novel Compound Heterozygous Mutation in TRAPPC9 Gene: The Relevance of Whole Genome Sequencing

Álvarez-Mora

Corominas

Gilissen

et al. 2021

Genes

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Advances in high-throughput technologies and its implementation worldwide have had a considerable impact on the elucidation of the molecular causes underlying neurodevelopmental psychiatric disorders, especially for autism spectrum disorder and intellectual disability (ID). Nevertheless, etiology remains elusive in close to 50% of cases, even in those families with multiple affected individuals, strongly hinting at a genetic cause. Here we present a case report of two siblings affected with severe ID and other comorbidities, who embarked on a genetic testing odyssey until diagnosis was reached by using whole genome sequencing (WGS). WGS identified a maternally inherited novel missense variant (NM_031466.7:c.1037G > A; p.Gly346Glu) and a paternally inherited 90 kb intragenic deletion in TRAPPC9 gene. This report demonstrates the clinical utility of WGS in patients who remain undiagnosed after whole exome sequencing.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Novel Compound Heterozygous Mutation in TRAPPC9 Gene: The Relevance of Whole Genome Sequencing

Álvarez-Mora

Corominas

Gilissen

et al. 2021

Genes

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“…In the present study, we provided evidence that the unmethylated TRAPPC9 promoter in region R2 is signi cantly correlated with higher concentration of NF-κB and cytokines in cow serum compared to the methylated cows. TRAPPC9 has been reported to be associated with some human diseases (liver disease and breast/colon cancer) [31]. Based on our results in vivo and in vitro, mRNA expression and methylation status of TRAPPC9 can be used to measure the healthy status of bovine udder, and CNVs and SNP2 in this gene can be regarded as the genetic basis of marker assistant selection for bovine mastitis resistance.…”

Section: Folic Acid Dose-dependently Prevents Mastitis and Increasesmentioning

confidence: 61%

Combined effects of intrinsic host gene (TRAPPC9) and extrinsic nutrient (folate) on resistance against S. aureus induced bovine mastitis

Mi¹,

Song²,

Dong³

et al. 2020

Preprint

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Background: Drug-resistance and immunological escape of Staphylococcus aureus and its “superbug”, methicillin-resistant S. aureus (MRSA), have become one of main causes of bacterial infection in both human and animals. In dairy cattle, elimination of bovine mastitis induced by S. aureus is of importance because S. aureus-infected cows normally are culled passively. Methods: Here, we investigated the beneficial effects of bovine trafficking protein particle complex 9 (TRAPPC9) gene and folic acid supplementation in the control of mastitis induced by S. aureus or MRSA by a series of in vivo and in vitro experiments. Results: The data showed that the genetic mutations and DNA methylation of TRAPPC9 were highly linked with the mastitis resistance of dairy cows. Additionally, knockdown of bovine TRAPPC9 was significantly involved in the mRNA expression levels of interleukin’s genes (increased IL-1β and IL-6), and down-regulated the protein level of NF-κB-P65 in the mastitis cell model induced by MRSA. Meanwhile, dose-dependent folic acid addition can inhibit the invasion of MRSA into Mac-T cells and improve TRAPPC9 expression in dairy cows. Conclusions: Altogether, our data suggest that an appropriate dose of folic acid can significantly reduce the inflammation caused by MRSA partially through TRAPPC9 mediated NF-κB pathway. These findings provide new insights to control the drug-resistant pathogens and to restrict the overuse of antibiotics through combined effects of the intrinsic host gene and extrinsic nutrient.

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“…After EPX treatment proteins involved in cytoskeleton arrangement or protein trafficking (TRAPPC9, SYNE1) were found to be significantly upregulated [83,84]. Together with upregulated proteins linked to inflammatory regulation, such as CD226 antigen, and STAT5B, as major regulator of signal transduction and transcriptional activation in response to cytokines, this might imply a potential regulation of receptor composition and immune related cell surface proteins or secreted factors [85,86].…”

Section: Discussionmentioning

confidence: 99%

The Mechanistic Differences in HLA-Associated Carbamazepine Hypersensitivity

et al. 2019

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Drug hypersensitivity reactions that resemble acute immune reactions are linked to certain human leucocyte antigen (HLA) alleles. Severe and life-threatening Stevens Johnson Syndrome and Toxic Epidermal Necrolysis following treatment with the antiepileptic and psychotropic drug Carbamazepine are associated with HLA-B*15:02; whereas carriers of HLA-A*31:01 develop milder symptoms. It is not understood how these immunogenic differences emerge genotype-specific. For HLA-B*15:02 an altered peptide presentation has been described following exposure to the main metabolite of carbamazepine that is binding to certain amino acids in the F pocket of the HLA molecule. The difference in the molecular mechanism of these diseases has not been comprehensively analyzed, yet; and is addressed in this study. Soluble HLA-technology was utilized to examine peptide presentation of HLA-A*31:01 in presence and absence of carbamazepine and its main metabolite and to examine the mode of peptide loading. Proteome analysis of drug-treated and untreated cells was performed. Alterations in sA*31:01-presented peptides after treatment with carbamazepine revealed different half-life times of peptide-HLA- or peptide-drug-HLA complexes. Together with observed changes in the proteome elicited through carbamazepine or its metabolite these results illustrate the mechanistic differences in carbamazepine hypersensitivity for HLA-A*31:01 or B*15:02 patients and constitute the bridge between pharmacology and pharmacogenetics for personalized therapeutics.

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TRAPPC9: Novel insights into its trafficking and signaling pathways in health and disease (Review)

Cited by 17 publications

References 43 publications

Novel Compound Heterozygous Mutation in TRAPPC9 Gene: The Relevance of Whole Genome Sequencing

Novel Compound Heterozygous Mutation in TRAPPC9 Gene: The Relevance of Whole Genome Sequencing

Combined effects of intrinsic host gene (TRAPPC9) and extrinsic nutrient (folate) on resistance against S. aureus induced bovine mastitis

The Mechanistic Differences in HLA-Associated Carbamazepine Hypersensitivity

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