Knockdown of SLC38 Transporter Ortholog – CG13743 Reveals a Metabolic Relevance in Drosophila

Aggarwal, Tanya; Patil, Sourabh; Ceder, Mikaela M.; Hayder, Maher; Fredriksson, Robert

doi:10.3389/fphys.2019.01592

Cited by 5 publications

(4 citation statements)

References 42 publications

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“…Disruptions in function of other members of the SLC38 family, such as SNAT3 in mouse (Chan et al, 2016 ) and SLC38A11 ortholog in D. melanogaster (Aggarwal et al, 2020 ), also affect body weight, indicating the importance of SLC38 transporters.…”

Section: Discussionmentioning

confidence: 99%

SLC38A10 Knockout Mice Display a Decreased Body Weight and an Increased Risk-Taking Behavior in the Open Field Test

Lindberg

Nordenankar

Fredriksson

2022

Front. Behav. Neurosci.

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The solute carrier 38 family (SLC38) is a family of 11 members. The most common substrate among these are alanine and glutamine, and members are present in a wide range of tissues with important functions for several biological processes, such as liver and brain function. Some of these transporters are better characterized than others and, in this paper, a behavioral characterization of SLC38A10−/− mice was carried out. A battery of tests for general activity, emotionality, motor function, and spatial memory was used. Among these tests, the elevated plus maze, Y-maze, marble burying and challenging beam walk have not been tested on the SLC38A10−/− mice previously, while the open field and the rotarod tests have been performed by the International Mouse Phenotyping Consortium (IMPC). Unlike the results from IMPC, the results from this study showed that SLC38A10−/− mice spend less time in the wall zone in the open field test than WT mice, implying that SLC38A10-deficient mice have an increased explorative behavior, which suggests an important function of SLC38A10 in brain. The present study also confirmed IMPC's data regarding rotarod performance and weight, showing that SLC38A10−/− mice do not have an affected motor coordination impairment and have a lower body weight than both SLC38A10+/− and SLC38A10+/+ mice. These results imply that a complete deficiency of the SLC38A10 protein might affect body weight homeostasis, but the underlying mechanisms needs to be studied further.

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Section: Discussionmentioning

confidence: 99%

SLC38A10 Knockout Mice Display a Decreased Body Weight and an Increased Risk-Taking Behavior in the Open Field Test

Lindberg

Nordenankar

Fredriksson

2022

Front. Behav. Neurosci.

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“…For example, MSLN is a target for CAR-T therapy that is currently being explored for CRC treatments (64). Furthermore, SLC38A11 may play a role in metabolism (61) and we identified a significant association between SLC38A11 expression and metastasis in our cohort, suggesting it may be of clinical relevance, especially in EOCRC patients. Combined, these eight genes produced a risk score significantly associated with decreased overall survival, and our data suggest that this risk score may be an independent prognostic indicator of CRC.…”

Section: Discussionmentioning

confidence: 66%

“…(B) Heatmap with PSI for tumor-enriched splice events predicted to bind the MHC I complex strongly in EOCRC normal and tumor samples. roles in other cancers (59,60), and SLC38A11 and WBSCR27 are relatively uncharacterized (61)(62)(63). All of these genes may give insight into EOCRC pathogenesis and serve as prognostic markers or predict different drug responses compared to LOCRC.…”

Section: Discussionmentioning

confidence: 99%

Identification of differentially expressed genes and splicing events in early-onset colorectal cancer

Marx,

Mankarious,

Koltun

et al. 2024

Front. Oncol.

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BackgroundThe incidence of colorectal cancer (CRC) has been steadily increasing in younger individuals over the past several decades for reasons that are incompletely defined. Identifying differences in gene expression profiles, or transcriptomes, in early-onset colorectal cancer (EOCRC, < 50 years old) patients versus later-onset colorectal cancer (LOCRC, > 50 years old) patients is one approach to understanding molecular and genetic features that distinguish EOCRC.MethodsWe performed RNA-sequencing (RNA-seq) to characterize the transcriptomes of patient-matched tumors and adjacent, uninvolved (normal) colonic segments from EOCRC (n=21) and LOCRC (n=22) patients. The EOCRC and LOCRC cohorts were matched for demographic and clinical characteristics. We used The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) database for validation. We used a series of computational and bioinformatic tools to identify EOCRC-specific differentially expressed genes, molecular pathways, predicted cell populations, differential gene splicing events, and predicted neoantigens.ResultsWe identified an eight-gene signature in EOCRC comprised of ALDOB, FBXL16, IL1RN, MSLN, RAC3, SLC38A11, WBSCR27 and WNT11, from which we developed a score predictive of overall CRC patient survival. On the entire set of genes identified in normal tissues and tumors, cell type deconvolution analysis predicted a differential abundance of immune and non-immune populations in EOCRC versus LOCRC. Gene set enrichment analysis identified increased expression of splicing machinery in EOCRC. We further found differences in alternative splicing (AS) events, including one within the long non-coding RNA, HOTAIRM1. Additional analysis of AS found seven events specific to EOCRC that encode potential neoantigens.ConclusionOur transcriptome analyses identified genetic and molecular features specific to EOCRC which may inform future screening, development of prognostic indicators, and novel drug targets.

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“…We also observed higher levels of SLC38A11 in alemtuzumab-treated patients experiencing a relapse, while the average expression decreased after each treatment course. SLC38A11 is a member of the SLC38 family of transmembrane sodium-coupled amino acid transporters, which are particularly expressed in cells that carry out significant amino acid metabolism [ 104 , 105 ]. However, its role in B cells and MS is still unclear.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome alterations in peripheral blood B cells of patients with multiple sclerosis receiving immune reconstitution therapy

Hecker

Fitzner

Boxberger

et al. 2023

J Neuroinflammation

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Background Multiple sclerosis (MS) is a chronic, inflammatory and neurodegenerative disease that leads to irreversible damage to the brain and spinal cord. The goal of so-called "immune reconstitution therapies" (IRTs) is to achieve long-term disease remission by eliminating a pathogenic immune repertoire through intense short-term immune cell depletion. B cells are major targets for effective immunotherapy in MS. Objectives The aim of this study was to analyze the gene expression pattern of B cells before and during IRT (i.e., before B-cell depletion and after B-cell repopulation) to better understand the therapeutic effects and to identify biomarker candidates of the clinical response to therapy. Methods B cells were obtained from blood samples of patients with relapsing–remitting MS (n = 50), patients with primary progressive MS (n = 13) as well as healthy controls (n = 28). The patients with relapsing MS received either monthly infusions of natalizumab (n = 29) or a pulsed IRT with alemtuzumab (n = 15) or cladribine (n = 6). B-cell subpopulation frequencies were determined by flow cytometry, and transcriptome profiling was performed using Clariom D arrays. Differentially expressed genes (DEGs) between the patient groups and controls were examined with regard to their functions and interactions. We also tested for differences in gene expression between patients with and without relapse following alemtuzumab administration. Results Patients treated with alemtuzumab or cladribine showed on average a > 20% lower proportion of memory B cells as compared to before IRT. This was paralleled by profound transcriptome shifts, with > 6000 significant DEGs after adjustment for multiple comparisons. The top DEGs were found to regulate apoptosis, cell adhesion and RNA processing, and the most highly connected nodes in the network of encoded proteins were ESR2, PHB and RC3H1. Higher mRNA levels of BCL2, IL13RA1 and SLC38A11 were seen in patients with relapse despite IRT, though these differences did not pass the false discovery rate correction. Conclusions We show that B cells circulating in the blood of patients with MS undergoing IRT present a distinct gene expression signature, and we delineated the associated biological processes and gene interactions. Moreover, we identified genes whose expression may be an indicator of relapse risk, but further studies are needed to verify their potential value as biomarkers.

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Knockdown of SLC38 Transporter Ortholog – CG13743 Reveals a Metabolic Relevance in Drosophila

Cited by 5 publications

References 42 publications

SLC38A10 Knockout Mice Display a Decreased Body Weight and an Increased Risk-Taking Behavior in the Open Field Test

SLC38A10 Knockout Mice Display a Decreased Body Weight and an Increased Risk-Taking Behavior in the Open Field Test

Identification of differentially expressed genes and splicing events in early-onset colorectal cancer

Transcriptome alterations in peripheral blood B cells of patients with multiple sclerosis receiving immune reconstitution therapy

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