The Nuclear Export and Dendritic Spine Localization of Transcriptional-regulator Spikar/ZMYND8

Abstract

Objective: The transcriptional regulator Spikar/ZMYND8 (Spikar) is a nucleus-associated protein, but in neurons it also binds to drebrin and localizes to dendritic spines. In this study, we identify the signaling region of Spikar that translocates to the cytoplasm from nucleus and clarify the stabilization mechanism of Spikar in the dendritic spine.

Methods: We transfected various GFP-fused Spikar mutant into cultured-cell to investigate their subcellular localization, aiming to identify the specific domain responsible for nuclear export. To examine the dependence of Spikar stabilization in dendritic spines on drebrin, we employed fluorescence recovery after photobleaching (FRAP) analysis in drebrin-knockdown neurons.

Results: The Coiled-Coil domain of Spikar played a pivotal role in mediating the process of nuclear export. FRAP analysis showed that the stable fraction of Spikar was reduced in the dendritic spines of drebrin knockdown neurons.

Conclusion: The coiled-coil region in the C-terminal region is important for the nuclear export of Spikar, and the drebrin-binding region in the N-terminal region is important for its stable localization in the dendritic spine.