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

Nazli Serin1,2, Gry H Dihazi3, Asima Tayyeb4

  • 1Clinic for Nephrology and Rheumatology, University Medical Center Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany.

International Journal of Molecular Sciences
|June 2, 2021
PubMed

Insights

Calreticulin (Calr) deficiency disrupts kidney development by impairing ribosome biogenesis and protein synthesis, hindering nephrogenesis. This study reveals Calr

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Nephrogenesis, the formation of kidneys, involves intricate signaling pathways controlling cell growth and differentiation.
  • Calreticulin (Calr), an endoplasmic reticulum chaperone, is known for calcium storage and glycoprotein folding, but its role in kidney development is unclear.

Purpose of the Study:

  • To investigate the role of Calreticulin (Calr) in mammalian kidney development (nephrogenesis).
  • To elucidate the molecular mechanisms underlying Calr's function in embryonic kidney formation.

Main Methods:

  • Utilized Calreticulin-deficient (Calr-/-) mouse models.
  • Employed proteomics and transcriptomics to analyze gene and protein expression.
  • Confirmed findings using CRISPR/cas9 mediated knockout.

Main Results:

  • Calr deficiency led to disrupted nephrogenic zone formation and retarded nephrogenesis, evidenced by abnormal comma- and s-shaped body development.
  • Proteomics and transcriptomics revealed impaired Wnt-signaling and reduced expression of ribosomal proteins in Calr-/- kidneys, indicating compromised protein synthesis.
  • CRISPR/cas9 confirmed Calr deficiency's link to deficiencies in ribosomal proteins and ribosome biogenesis.

Conclusions:

  • Calreticulin plays a critical role in regulating nephrogenesis.
  • Calr deficiency impairs kidney development by disrupting ribosome biogenesis and protein synthesis.
  • A direct link exists between Calreticulin expression and ribosome biogenesis during kidney development.
Keywords:
calreticulin deficiencynephrogenesisribosomal biogenesis

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