Activity-dependent subcellular cotrafficking of the small GTPase Rem2 and Ca2+/CaM-dependent protein kinase IIα.

Publication Type:

Journal Article


PLoS One, Volume 7, Issue 7, p.e41185 (2012)


Animals, Calcium, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Cell Line, DNA, Epitopes, Gene Expression Regulation, GTP-Binding Proteins, HEK293 Cells, Hippocampus, Humans, Microscopy, Fluorescence, Monomeric GTP-Binding Proteins, Neuronal Plasticity, Neurons, Protein Binding, Protein Structure, Tertiary, Protein Transport, Rats, Receptors, N-Methyl-D-Aspartate


<p><b>BACKGROUND: </b>Rem2 is a small monomeric GTP-binding protein of the RGK family, whose known functions are modulation of calcium channel currents and alterations of cytoskeletal architecture. Rem2 is the only RGK protein found predominantly in the brain, where it has been linked to synaptic development. We wished to determine the effect of neuronal activity on the subcellular distribution of Rem2 and its interacting partners.</p><p><b>RESULTS: </b>We show that Rem2 undergoes activity-and N-Methyl-D-Aspartate Receptor (NMDAR)-dependent translocation in rat hippocampal neurons. This redistribution of Rem2, from a diffuse pattern to one that is highly punctate, is dependent on Ca(2+) influx, on binding to calmodulin (CaM), and also involves an auto-inhibitory domain within the Rem2 distal C-terminus region. We found that Rem2 can bind to Ca(2+)/CaM-dependent protein kinase IIα (CaMKII) a in Ca(2+)/CaM-dependent manner. Furthermore, our data reveal a spatial and temporal correlation between NMDAR-dependent clustering of Rem2 and CaMKII in neurons, indicating co-assembly and co-trafficking in neurons. Finally, we show that inhibiting CaMKII aggregation in neurons and HEK cells reduces Rem2 clustering, and that Rem2 affects the baseline distribution of CaMKII in HEK cells.</p><p><b>CONCLUSIONS: </b>Our data suggest a novel function for Rem2 in co-trafficking with CaMKII, and thus potentially expose a role in neuronal plasticity.</p>

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