Following OGD/R, annexin 1 nuclear translocation and subsequent induction of apoptosis in neurons are assisted by myosin IIA in a TRPM7 kinase-dependent manner

Mol Neurobiol. 2015 Apr;51(2):729-42. doi: 10.1007/s12035-014-8781-y. Epub 2014 Jun 18.


Transient receptor potential cation channel, subfamily M, member 7 (TRPM7) is a bifunctional channel protein that contains an α-kinase domain at its C-terminal. Previous studies have indicated that oxygen-glucose deprivation/reoxygenation (OGD/R) induces neuronal apoptosis via TRPM7. Annexin 1 and myosin IIA have been identified as TRPM7 kinase substrates; however, the role of annexin 1 in OGD/R-induced neuron apoptosis remains unclear. Here, we report that OGD/R induces nuclear translocation of annexin 1 in primary cultured neurons. Interestingly, ablation of the TRPM7 kinase or a point mutation in Ser(5) interferes with TRPM7 kinase-annexin 1 binding, decreasing annexin 1 nuclear translocation, and thereby reducing neuronal apoptosis. Furthermore, mutation of Arg(205), which intercepts annexin 1-formyl peptide receptor binding, also decreased annexin 1 nuclear translocation. Coimmunoprecipitation indicated that annexin 1 is moved as cargo through the cytoplasm by myosin IIA. However, inhibiting myosin IIA can decrease annexin 1 nuclear translocation. Moreover, blocking myosin IIA function by antagonist injection into the lateral ventricle was found to improve learning and memory in rats after middle cerebral artery occlusion and could also improve cell viability after OGD/R. Last, we determined that the annexin 1-myosin IIA complex is recognized and translocated by the importin α/β heterodimer. Therefore, TRPM7 kinase modulates OGD/R-induced neuronal apoptosis via annexin 1 carried by myosin IIA, while nuclear formyl peptide receptor (FPR)-annexin 1 binding and importin β are involved in nuclear translocation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / physiology*
  • Animals
  • Annexin A1 / metabolism*
  • Apoptosis / physiology
  • Cell Hypoxia / physiology
  • Cells, Cultured
  • Glucose / deficiency*
  • HEK293 Cells
  • Humans
  • Male
  • Neurons / metabolism*
  • Nonmuscle Myosin Type IIA / metabolism*
  • Oxygen / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • TRPM Cation Channels / metabolism*


  • Annexin A1
  • TRPM Cation Channels
  • Trpm7 protein, rat
  • Nonmuscle Myosin Type IIA
  • Glucose
  • Oxygen