Molecular Neurobiology

, Volume 56, Issue 5, pp 3368–3379 | Cite as

Degradation of Caytaxin Causes Learning and Memory Deficits via Activation of DAPK1 in Aging

  • Yu Guo
  • Hao Li
  • Xiao Ke
  • Manfei Deng
  • Zhuoze Wu
  • You Cai
  • Henok Kessete Afewerky
  • Xiaoan Zhang
  • Lei PeiEmail author
  • Youming LuEmail author


Loss of memory is an inevitable clinic sign in aging, but its underlying mechanisms remain unclear. Here we show that death-associated protein kinase (DAPK1) is involved in the decays of learning and memory in aging via degradation of Caytaxin, a brain-specific member of BNIP-2. DAPK1 becomes activated in the hippocampus of mice during aging. Activation of DAPK1 is closely associated with degradation of Caytaxin protein. Silencing Caytaxin by the expression of small interfering RNA (siRNA) that targets specifically to Caytaxin in the hippocampus of adult mice impairs the learning and memory. Genetic inactivation of DAPK1 by deletion of DAPK1 kinase domain prevents the degradation of Caytaxin and protects against learning and memory declines. Thus, activation of DAPK1 impairs learning and memory by degrading Caytaxin during aging.


DAPK1 Caytaxin Aging Learning and memory 



death-associated protein kinase 1




long-term potentiation




miniature excitatory post synaptic current


Author Contributions

YL and LP conceived and designed the studies and wrote the paper. YG and HL carried out the experiments including western blot, qPCR, and mutagenesis and virus construction and behavioral studies. XK and MD performed electrophysiological studies and immunohistochemistry. YC, ZW, HKA, and XZ performed the experiments including genotyping, PCR, and animal breeding. All authors contributed to the data analysis and presentation in the paper.

Funding Information

This project was supported by the National Natural Science Foundation of China (Grant No. 31721002 to YL; 91632306 to YL; 51627807 to YL; 81571078 to LP) and the Medjaden Academy & Research Foundation for Young Scientists (Grant No. MJR20160057).

Compliance with Ethical Standards

All mice used in this study were bred and reared in the same conditions in accordance with institutional guidelines of the Animal Care and Use Committee (Huazhong University of Science and Technology, Wuhan, China) within the University’ s animal care facility.

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Physiology, School of Basic Medicine and Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  2. 2.The Institute for Brain Research, Collaborative Innovation Center for Brain ScienceHuazhong University of Science and TechnologyWuhanChina
  3. 3.Department of Pathology and Pathophysiology, School of Basic Medicine and Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  4. 4.Department of Neurobiology, School of Basic Medicine and Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

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