title: Hippocampal LTP triggers proteasome-mediated SPAR degradation in CA1 neurons.
abstract: Activity-dependent synaptic plasticity is associated with synaptic protein turnover involving the ubiquitin proteasome system (UPS) for protein degradation. In primary hippocampal cell culture, it has been shown that increased or decreased activity of synaptic transmission can regulate the amount of postsynaptic density (PSD) proteins via UPS. However, the specific spatio-temporal dynamic of PSD protein degradation after LTP induction and its downstream signaling pathways remains to be clarify. We used confocal microscopy to monitor levels of eGFP-tagged SPAR (spine-associated Rap GTPase activating protein) expressed in acute hippocampal slices and found that LTP induction triggered a UPS-dependent decay of eGFP-SPAR fluorescence. SPAR degradation was reduced upon inhibition of cyclin-dependent kinase 5 (CDK5) as well as by a protein synthesis inhibitor. Comparison of eGFP-tagged SPAR levels with those obtained in control experiments with eGFP revealed a protein synthesis-independent component of LTP-associated SPAR degradation. This second component required UPS and NMDA receptor activation but not CDK5. We conclude that LTP triggers a down regulation of SPAR by two complementary mechanisms, one of which has previously been described to mediate homeostatic plasticity.
authors: Institutes of Brain Science, Fudan University, Shanghai 200032, People's Republic of China.
authors: Ying
authors: Y
authors: Chen
authors: Pingan
authors: P
authors: Yuanxiang
authors: Thomas
authors: T
authors: Knöpfel
authors: Ulrich
authors: U
authors: Thomas
authors: Thomas
authors: T
authors: Behnisch
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D051360:Cyclin-Dependent Kinase 5 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology*; D020690:GTPase-Activating Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000502:physiology*; D009474:Neurons / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D009924:Organ Culture Techniques; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020690:GTPase-Activating Proteins; D011500:Protein Synthesis Inhibitors; C479629:Sipa1l1 protein, rat; D051360:Cyclin-Dependent Kinase 5; C495907:Cdk5 protein, rat; D046988:Proteasome Endopeptidase Complex