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Calpain A modulates Toll responses by limited Cactus/IκB proteolysis

Marcio Fontenele1, Bomyi Lim, Danielle Oliveira

  • 1Institute for Biomedical Sciences, Federal University of Rio de Janeiro, CEP 21941-902 Rio de Janeiro, Brazil Chemistry Institute, Federal University of Rio de Janeiro, CEP 21941-902 Rio de Janeiro, Brazil Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular, Rio de Janeiro, Brazil Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544 Princeton Collaborative Proteomics and Mass Spectrometry Center, Princeton University, Princeton, NJ 08544 Molecular Biology Department, Princeton University, Princeton, NJ 08544 Howard Hughes Medical Institute, Chevy Chase, MD 20815.

Molecular Biology of the Cell
|July 19, 2013
PubMed

Insights

Calpain A protease modifies the Cactus protein in fruit flies, impacting NF-kappaB signaling. This protease generates fragments that alter how Toll-responsive pathways function in embryos and the immune system.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Cellular Biology

Background:

  • Calpains are calcium-dependent proteases that modulate protein function through limited proteolysis.
  • Calpains target IκB proteins, which are key regulators of NFκB transcription factors.
  • Understanding calpain's role in IκB regulation is crucial for comprehending NFκB pathway modulation.

Purpose of the Study:

  • To investigate the in vivo interaction and function of Calpain A (CalpA) on the Drosophila melanogaster IκB homologue, Cactus.
  • To elucidate the mechanisms by which CalpA regulates NFκB activity through Cactus modification.

Main Methods:

  • In vivo studies using Drosophila melanogaster models.
  • Analysis of protein-protein interactions between CalpA and Cactus.
  • Characterization of Cactus protein fragments generated by CalpA cleavage.

Main Results:

  • CalpA alters the total amount of Cactus protein.
  • CalpA physically interacts with Cactus, specifically targeting the pool not bound to Dorsal.
  • Proteolytic cleavage by CalpA produces Cactus fragments lacking the N-terminal Toll responsiveness region.
  • These fragments exhibit distinct properties compared to full-length Cactus.

Conclusions:

  • CalpA targets free Cactus, modulating its function.
  • CalpA-generated Cactus fragments play a role in Toll-responsive complexes within the Drosophila embryo and immune system.
  • CalpA represents a novel regulatory mechanism for NFκB signaling via Cactus processing.

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