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| Status |
Public on Oct 01, 2022 |
| Title |
A previously uncharacterized Kidney-Associated Membrane Protein (KAMP) is associated with evolutionary adaptation, energy balance and kidney physiology |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
During the evolution of vertebrates, specific molecular innovations ensured adaptations which resulted in the split of different animal groups. Here comparative genomic analysis became a valued instrument to identify genes associated with the divergence of taxa and speciation events. Using this approach, we identified the association of the previously uncharacterized gene (mouse (1700011H14RIK, human C14ORF105/CCDC198), hereby named Kamp (Kidney-associated membrane protein) with the evolutionary split leading to birds and mammals. Furthermore, by comparing single nuclear polymorphisms of modern humans with Neandertals at the locus of Kamp, we identified gene-flow of Kamp from Neandertals into modern humans. Analyzing the expression of Kamp in humans revealed a restriction to the kidney, pancreas, and few other organs. A knockout of this gene in mice resulted in a structurally normal kidney as validated with micro-computed microtomography scans and single-cell transcriptomics, but with higher Albumin levels in the urine lower serum ferritin levels. Further, interactomics screening revealed an interaction between KAMP and ferritin (heavy chain), which was cross-validated by the analysis of co-localization of both proteins in vesicular and plasma membranes. The membranal localization of KAMP appeared regulated by its N-terminal myristoylation site, as KAMP became cytoplasmic in the absence of this specific sequence. Kamp knockout animals demonstrated increased body weight and decreased energy expenditure. This corresponded to Genome-Wide Association Studies of Kamp linked with higher BMI, diabetes-related pathologies, and macular degeneration in humans. Subsequent gain-of-function experiments showed altered proliferative dynamics and accumulation of KAMP during mitosis. Bioinformatics analysis indicated a protective role of KAMP in renal and liver cancer progression, as suggested by an association of KAMP with epithelial-to-mesenchymal transition and altered localization in tumors versus healthy tissue. Altogether, our results revealed several important roles played by KAMP in a vertebrate body, with specific emphasis on metabolite excretion and energy expenditure.
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| Overall design |
The kidneys of widltype and KAMP knock-out mutant littermate mice (both male and female) were dissected out, dissociated and then subjected to single cell transcriptomics sequencing using 10x Chromium approach.
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| Contributor(s) |
Petersen J, Artemov A, Poverennaya I, Kastriti ME, Bouderlique TG, Adameyko I |
| Citation(s) |
37248239 |
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| Submission date |
Jun 24, 2022 |
| Last update date |
Aug 30, 2023 |
| Contact name |
Irina Poverennaya |
| E-mail(s) |
irina.poverennaya@meduniwien.ac.at
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| Organization name |
Medical University of Vienna
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| Department |
Neuroimmunology
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| Street address |
Spitalgasse 4 / Medizinishe Universitat Wien, Zentrum fur Hirnforschung
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| City |
Vienna |
| State/province |
Österreich |
| ZIP/Postal code |
1090 |
| Country |
Austria |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (5)
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| Relations |
| BioProject |
PRJNA852522 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE206860_RAW.tar |
40.1 Mb |
(http)(custom) |
TAR (of H5) |
| GSE206860_UMAP_embedding.csv.gz |
335.4 Kb |
(ftp)(http) |
CSV |
| GSE206860_annotation.tsv.gz |
353.7 Kb |
(ftp)(http) |
TSV |
| GSE206860_count_matrix.tsv.gz |
22.1 Mb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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