|Comment by Chunjiang Yu and Mary Jo LaDu
In this paper, Yadong Huang and his colleagues identify a regulatory mechanism, relatively common for other genes, that is unique in its application to ApoE. In so doing, this work also addresses the long-standing controversy of whether neurons express ApoE. The authors demonstrate that ApoE is constitutively expressed in hippocampal neurons but retained in their nuclei because of alternative splicing of intron 3. Conditioned media from rat C6 cells (a glial-derived cell line) in vitro, or kainic acid treatment in vivo, results in the splicing of intron 3 and export of mature ApoE mRNA from the nucleus to the cytosol for translation. These results provide a nice molecular interpretation of the early work by this group (2), which showed that conditioned media from C6 cells or ApoE-KO mouse primary glia regulate neuronal ApoE expression (RT-PCR, WB) in stable N2a lines, NT2 cells, and mouse primary neurons.
However, to these readers, at least, these results are in apparent contrast to the group’s earlier work using ApoE-EGFP...