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CD2AP/CIN85 balance determines receptor tyrosine kinase signaling response in podocytes

Irini Tossidou1, Christian Kardinal, Imke Peters

  • 1Division of Nephrology, Department of Medicine, and Division of Pediatric Hematology and Oncology, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany.

The Journal of Biological Chemistry
|January 11, 2007
PubMed

Insights

Defects in CD2-associated protein (CD2AP) disrupt kidney podocyte signaling, causing nephrotic syndrome. Maintaining the CD2AP/CIN85 protein balance is crucial for normal podocyte function and preventing kidney disease.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cellular Signaling

Background:

  • Podocyte signaling defects underlie inherited glomerular diseases and glomerulosclerosis.
  • CD2-associated protein (CD2AP) is vital for podocyte function and glomerular slit diaphragm integrity.

Purpose of the Study:

  • To investigate the role of CD2AP in intracellular signaling pathways within kidney podocytes.
  • To elucidate the mechanism behind delayed podocyte injury in CD2AP-deficient mice.

Main Methods:

  • Utilized CD2AP-deficient (CD2AP(-/-)) mice to study podocyte signaling.
  • Analyzed receptor tyrosine kinase (RTK) signaling, including phosphatidylinositol 3-kinase/AKT and ERK pathways.
  • Assessed the expression and function of CIN85 in CD2AP(-/-) podocytes both in vitro and in vivo.

Main Results:

  • CD2AP deficiency impairs RTK signaling initiation and termination in podocytes.
  • Increased CIN85 protein in CD2AP(-/-) podocytes leads to diminished growth factor-induced signaling.
  • Restored RTK signaling was observed upon repression of CIN85, highlighting its role in CD2AP(-/-) podocytes.

Conclusions:

  • Impaired intracellular signaling and podocyte damage result from CD2AP deficiency.
  • The balance between CD2AP and CIN85 proteins is critical for normal podocyte RTK signaling.
  • Dysregulation of this balance contributes to the pathogenesis of nephrotic syndrome.

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