Post-translational modification of proteins by the small ubiquitin-like modifiers (SUMOs) has emerged as an important regulatory mechanism for alteration of protein activity, stability, and cellular localization. It has been reported that SUMOylation plays an important role in some activities of neuronal cells. However, the link between SUMOylation and activity-de pendent stimuli of neurons remains to be elucidated. Here we showed that KCl-induced depolarization increased SUMO conjugation in SHSY5Y cell line in a time-dependent manner. The increase of SUMOylation was largely dependent oil calcium influx and intracellular calcium signals. Our study demonstrates the link between the activity-dependent stimuli and global SUMOs conjugation, which may play an important role in activity-dependent signals of neurons. (C) 2009 Elsevier Inc. All rights reserved.