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Gene expression pattern in PC12 cells with reduced PMCA2 or PMCA3 isoform: selective up-regulation of calmodulin and

Tomasz Boczek1, Anna Kozaczuk, Bozena Ferenc

  • 1Department of Molecular Neurochemistry, Medical University, Lodz, Poland.

Molecular and Cellular Biochemistry
|September 14, 2011
PubMed

Insights

Reducing neuron-specific plasma membrane calcium pump (PMCA) isoforms in PC12 cells alters gene expression and signaling pathways. This adaptation helps cells manage increased cytosolic calcium levels and affects cell morphology and neuritogenesis.

Area of Science:

  • Cell Biology
  • Neuroscience
  • Biochemistry

Background:

  • Cellular calcium homeostasis is primarily regulated by the plasma membrane calcium pump (PMCA).
  • Four PMCA isoforms exist, with PMCA1 and PMCA4 being ubiquitous and PMCA2/PMCA3 found in excitable cells.
  • Previous studies indicated that suppressing neuron-specific PMCAs in PC12 cells induces morphological changes and neuritogenesis.

Purpose of the Study:

  • To investigate the impact of reducing PMCA2 or PMCA3 expression in PC12 cells on gene expression.
  • To analyze the effects on key signaling molecules including calmodulin (CaM), neuromodulin (GAP43), and MAP kinases.
  • To understand how PMCA isoform suppression influences cellular adaptation to elevated cytosolic calcium.

Main Methods:

  • Utilized microarrays, real-time PCR, and immunodetection techniques.
  • Analyzed gene and protein expression levels of CaM, GAP43, and various MAP kinases (ERK, p38, JNK).
  • Compared control PC12 cells with lines exhibiting reduced PMCA2 or PMCA3 expression.

Main Results:

  • PMCA suppression led to increased total calmodulin (CaM) due to elevated calm I and calm II gene expression.
  • Neuromodulin (GAP43) mRNA and protein levels rose, but its phosphorylation decreased.
  • Alterations were observed in the localization of CaM/GAP43 and CaM/pGAP43 complexes.
  • ERK1/2 levels increased, with decreased pERK1 and unchanged pERK2.
  • p38 phosphorylation diminished, while JNK2 protein decreased without affecting pJNK levels.
  • Microarray analysis revealed distinct expression patterns in genes related to cell cycle, proliferation, migration, differentiation, apoptosis, and signaling.

Conclusions:

  • Suppression of neuron-specific PMCA isoforms (PMCA2/PMCA3) in PC12 cells significantly impacts gene expression and signaling pathways.
  • These changes enable PC12 cells to adapt to sustained increases in cytosolic calcium concentration.
  • This study provides the first evidence for the role of PMCA2 and PMCA3 in regulating signaling pathways within PC12 cells.

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