Hippocalcin mediates calcium-dependent translocation of brain-type creatine kinase (BB-CK) in hippocampal neurons

Masaaki Kobayashi1, Makoto Hamanoue, Tamotsu Masaki

  • 1Department of Physiology, Toho University School of Medicine, Ohmori-nishi 5-21-16, Ohta-ku, Tokyo 143-8540, Japan.

Insights

Hippocalcin (Hpca) binds to brain-type creatine kinase (BB-CK) in a calcium-dependent manner. This interaction facilitates the translocation of BB-CK to cellular membranes, impacting neuronal function.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Hippocalcin (Hpca) is a calcium-binding protein crucial for neuronal plasticity.
  • Brain-type creatine kinase (BB-CK) plays a vital role in cellular energy metabolism within neurons.

Purpose of the Study:

  • To investigate the interaction between Hippocalcin (Hpca) and creatine kinase subunits.
  • To elucidate the role of Hpca in the cellular localization of BB-CK.

Main Methods:

  • Protein purification and identification from rat brain.
  • In vitro binding assays to determine protein-protein interactions.
  • Cell culture experiments with hippocampal neurons and ionomycin treatment.

Main Results:

  • Hippocalcin (Hpca) specifically binds to the creatine kinase B (CKB) subunit in a calcium-dependent manner.
  • Hpca mediates the partial translocation of CKB to membranes, dependent on N-myristoylation.
  • Colocalization of Hpca and CKB near the plasma membrane was observed in neurons upon calcium stimulation.

Conclusions:

  • Hippocalcin (Hpca) forms a complex with brain-type creatine kinase (BB-CK).
  • The Hpca-BB-CK complex translocates to membrane compartments in response to calcium signaling.
  • This interaction suggests a novel regulatory mechanism for BB-CK localization and function in neurons.