| Abstract No.: | A-B1071 |
| Country: | Canada |
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| Title: | RETENTION OF ALPHA-CAMKII AT POSTSYNAPTIC SITES REQUIRES SPECIFIC ACTIVATION OF SYNAPTIC NMDA RECEPTORS AND ACTIVITY OF THE SRC KINASE FAMILY |
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| Authors/Affiliations: | 1 Mado Lemieux*; 1 Éric LeBel; 1 Christian Tardif; 1 Amélie Forest; 1 Paul De Koninck;
1 Laval University/CRULRG, Québec, QC, Canada
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| Content: | Objectives: Input-specific synaptic plasticity is thought to involve an activity-dependent and synaptic-specific recruitment of proteins that affect synaptic strength. Little is known about the signals that can elicit long-lasting and input-specific recruitment of synaptic elements and how such elements can be maintained at the synapse in the face of ongoing protein degradation. In this study, we looked at mechanisms implicated in the retention of CaMKII at postsynaptic sites following activity. CaMKII is a key enzyme in activity-dependent synaptic plasticity that can be recruited postsynaptically for short or long periods of time in response to NMDA receptor activation.
Materials and Methods: In primary hippocampal neurons in culture, we did time-lapse imaging of alpha-CaMKII, calmodulin and Ca2+. We also used immunocytochemistry and Fluorescence Recovery After Photobleaching (FRAP) techniques.
Results: We show that the longlasting retention of alpha-CaMKII to postsynaptic sites increased with synaptic maturation, but depended modestly on the geometry of the synapse and did not require the integrity of cytoskeletal elements. We demonstrate that Ca2+ influx through NMDA receptors specifically located at synapses, but not from other sources, was required to lock alpha-CaMKII in postsynaptic compartments. However, this retention did not require that CaMKII activity, free Ca2+ or calmodulin levels remain above baseline in postsynaptic sites. The activity of tyrosine kinase Src family was required to lock alpha-CaMKII after its translocation to mature synapses. In contrast, inhibiting calpain activity increased the fraction of alpha-CaMKII locked postsynaptically, even in immature synapses or in presence of Src inhibitors. Conclusions: These results suggest that a local Ca2+ influx through synaptic NMDA receptors is necessary to elicit the persistent binding of alpha-CaMKII postsynaptically and that Src activity protects calpain-dependent removal of the enzyme. Thus, input-specific and Src-dependent maintenance of alpha-CaMKII to synaptic sites could serve as mechanisms to support long term potentiation of synaptic transmission. |
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