Abstract
Serum inducible kinase (SNK), also known as polo-like kinase 2 (PLK2), is a known regulator of mitosis, synaptogenesis and synaptic homeostasis. However, its role in early cortical development is unknown. Herein, we show that snk is expressed in the cortical plate from embryonic day 14, but not in the ventricular/subventricular zones (VZ/SVZ), and SNK protein localizes to the soma and dendrites of cultured immature cortical neurons. Loss of SNK impaired dendritic but not axonal arborization in a dose-dependent manner and overexpression had opposite effects, both in vitro and in vivo. Overexpression of SNK also caused abnormal branching of the leading process of migrating cortical neurons in electroporated cortices. The kinase activity was necessary for these effects. Extracellular signal-regulated kinase (ERK) pathway activity downstream of brain-derived neurotrophic factor (BDNF) stimulation led to increases in SNK protein expression via transcriptional regulation, and this upregulation was necessary for the growth-promoting effect of BDNF on dendritic arborization. Taken together, our results indicate that SNK is essential for dendrite morphogenesis in cortical neurons.
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Acknowledgements
We thank Dr Xiao-Bing Yuan and members of his lab (Institute of Neuroscience, SIBS, CAS, China) for offering the use of their in vitro electroporation system. We also thank Chi Zhang (Institute of Neuroscience, SIBS, CAS, China) for her assistance with our cell culture procedures, as well as Bing-Fa Sun (Institute of Biochemistry and Cell Biology, SIBS, CAS, China) and Da-Feng Xu (East China University of Science and Technology, China) for assistance with our cloning procedures. This work was supported by grants from the 973 Program (2011CBA00407), NSFC (30925016; 31021063) and the Chinese Academy of Sciences (XDA01020305).
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(Supplementary information is linked to the online version of the paper on the Cell Research website.)
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Supplementary information, Figure S1
SNK expression in the developing cortex and subcellular localization of SNKK108M in DIV3 cortical neurons. (PDF 105 kb)
Supplementary information, Figure S2
shRNA-scr has no effect on dendritic arborization. (PDF 42 kb)
Supplementary information, Figure S3
Knockdown efficiency of SNK shRNA constructs in DIV3 neurons. (PDF 116 kb)
Supplementary information, Figure S4
U73122 blocks PLCγ phosphorylation. (PDF 28 kb)
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Guo, SL., Tan, GH., Li, S. et al. Serum inducible kinase is a positive regulator of cortical dendrite development and is required for BDNF-promoted dendritic arborization. Cell Res 22, 387–398 (2012). https://doi.org/10.1038/cr.2011.100
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DOI: https://doi.org/10.1038/cr.2011.100
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