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

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.External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c

Zhao, Y., Wang, J., Jiang, H., Yu, Z., Li, X., Shi, J.,
["Department of Neurobiology and Key Laboratory of Neurological Disease of Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, People's Republic of China."]
Transient receptor potential cation channel, subfamily M, member 7 (TRPM7) is a bifunctional channel protein that contains an alpha-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 alpha/beta 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 beta are involved in nuclear translocation.
PMID: 24939696External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c
Validation: In vivo validation Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Assay with endogenous proteins Assay with overexpressed proteins Reference
Cell or tissue Cell or tissue TRP channel construct Interactor construct
TRP channel Interactor Method Species Region Species Region
TRPM7 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Annexin 1 Co-immunoprecipitation HEK293 Human ChaK1 domain Human Not determined 24939696
TRPM7 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Annexin 1 Co-immunofluorescence staining HEK293 Human ChaK1 domain Human Not determined 24939696
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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