title: Differential regulation of proteasome activity in the nucleus and the synaptic terminals.
abstract: Proteasome is a multi-subunit proteolytic complex that degrades proteins covalently linked to multiple molecules of ubiquitin. Earlier studies showed a role for the ubiquitin-proteasome pathway in several models of long-term memory and other forms of synaptic plasticity. In Aplysia, the ubiquitin-proteasome pathway has been shown to contribute to the induction of long-term facilitation. In other model systems, ubiquitin-proteasome-mediated proteolysis has also been shown to play a role in synapse development. Previous studies of synaptic plasticity focused on changes in components or the substrates of the ubiquitin-proteasome pathway in whole neurons. Modification of specific synapses would require precise spatial and temporal regulation of the components of the ubiquitin-proteasome pathway within the subcellular compartments of neurons during learning. As a first step towards testing the idea of local regulation of the ubiquitin-proteasome pathway in neurons, we investigated proteasome activity in nuclear and synaptosomal fractions. Here we show that proteasome activity in the synaptic terminals is higher compared to the activity in the nucleus in the Aplysia nervous system as well as in the mouse brain. Furthermore, the proteasome activity in the two neuronal compartments is differentially modulated by protein kinases. Differential regulation of proteasome activity in neuronal compartments such as the synaptic terminals is likely to be a key mechanism underlying synapse-specific plasticity.
authors.affiliation: Department of Neurobiology and Anatomy, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC, USA.
authors.forename: Sudarshan C
authors.initials: SC
authors.lastname: Upadhya
authors.forename: Lan
authors.initials: L
authors.lastname: Ding
authors.forename: Thuy K
authors.initials: TK
authors.lastname: Smith
authors.forename: Ashok N
authors.initials: AN
authors.lastname: Hegde
mesh_terms: D000818:Animals; D001048:Aplysia; D002467:Cell Nucleus / Q000201:enzymology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000201:enzymology; D017729:Presynaptic Terminals / Q000201:enzymology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011494:Protein Kinases / Q000502:physiology; D012701:Serotonin / Q000502:physiology; D013574:Synaptosomes / Q000201:enzymology
chemical_list: D012701:Serotonin; D011494:Protein Kinases; D046988:Proteasome Endopeptidase Complex