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Publication : Calreticulin Deficiency Disturbs Ribosome Biogenesis and Results in Retardation in Embryonic Kidney Development.

First Author  Serin N Year  2021
Journal  Int J Mol Sci Volume  22
Issue  11 PubMed ID  34070742
Mgi Jnum  J:308971 Mgi Id  MGI:6751102
Doi  10.3390/ijms22115858 Citation  Serin N, et al. (2021) Calreticulin Deficiency Disturbs Ribosome Biogenesis and Results in Retardation in Embryonic Kidney Development. Int J Mol Sci 22(11)
abstractText  Nephrogenesis is driven by complex signaling pathways that control cell growth and differentiation. The endoplasmic reticulum chaperone calreticulin (Calr) is well known for its function in calcium storage and in the folding of glycoproteins. Its role in kidney development is still not understood. We provide evidence for a pivotal role of Calr in nephrogenesis in this investigation. We show that Calr deficiency results in the disrupted formation of an intact nephrogenic zone and in retardation of nephrogenesis, as evidenced by the disturbance in the formation of comma-shaped and s-shaped bodies. Using proteomics and transcriptomics approaches, we demonstrated that in addition to an alteration in Wnt-signaling key proteins, embryonic kidneys from Calr(-/-) showed an overall impairment in expression of ribosomal proteins which reveals disturbances in protein synthesis and nephrogenesis. CRISPR/cas9 mediated knockout confirmed that Calr deficiency is associated with a deficiency of several ribosomal proteins and key proteins in ribosome biogenesis. Our data highlights a direct link between Calr expression and the ribosome biogenesis.
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