title: Two inhibitors of the ubiquitin proteasome system enhance long-term memory formation upon olfactory conditioning in the honeybee (Apis mellifera).
abstract: In honeybees (Apis mellifera), the proteasome inhibitor Z-Leu-Leu-Leu-CHO (MG132) enhances long-term memory (LTM) formation. Studies in vertebrates using different inhibitors of the proteasome demonstrate the opposite, namely an inhibition of memory formation. The reason for this contradiction remains unclear. MG132 is an inhibitor of the proteasome, but also blocks other proteases. Accordingly, one possible explanation might be that other proteases affected by MG132 are responsible for the enhancement of LTM formation. We test this hypothesis by comparing the effect of MG132 and the more specific proteasome inhibitor clasto-lactacystin beta-lactone (β-lactone). We show that these two inhibitors block the activity of the proteasome in honeybee brains to a similar extent, do not affect the animals' survival but do enhance LTM retention upon olfactory conditioning. Thus, the enhancement of LTM formation is not due to MG132-specific side effects, but to inhibition of a protease targeted by MG132 and β-lactone, i.e. the proteasome.
authors: Freie Universität Berlin, FB Biologie, Pharmazie, Chemie, Institut für Biologie, Neurobiologie, Königin-Luise-Strasse 28/30, 14195 Berlin, Germany.
authors: Johannes
authors: J
authors: Felsenberg
authors: Freie Universität Berlin, FB Biologie, Pharmazie, Chemie, Institut für Biologie, Neurobiologie, Königin-Luise-Strasse 28/30, 14195 Berlin, Germany.
authors: Yan
authors: Y
authors: Dyck
authors: Institut für Biochemie, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors: Alexander
authors: A
authors: Kloß
authors: Institut für Biochemie, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors: Burkhardt
authors: B
authors: Dahlmann
authors: Institut für Biochemie, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors: Peter-Michael
authors: PM
authors: Kloetzel
authors: Freie Universität Berlin, FB Biologie, Pharmazie, Chemie, Institut für Biologie, Neurobiologie, Königin-Luise-Strasse 28/30, 14195 Berlin, Germany dorothea.eisenhardt@fu-berlin.de.
authors: Dorothea
authors: D
authors: Eisenhardt
mesh_terms: D000818:Animals; D001516:Bees / Q000187:drug effects / Q000502:physiology*; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D007783:Lactones / Q000378:metabolism / Q000494:pharmacology; D007976:Leupeptins / Q000378:metabolism / Q000494:pharmacology; D057567:Memory, Long-Term / Q000187:drug effects / Q000502:physiology*; D009812:Odorants; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D061988:Proteasome Inhibitors / Q000494:pharmacology*; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D007783:Lactones; D007976:Leupeptins; D009842:Oligopeptides; D061988:Proteasome Inhibitors; D025801:Ubiquitin; C098869:clasto-lactacystin beta-lactone; D046988:Proteasome Endopeptidase Complex; C036671:leucyl-leucyl-leucine; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde
keywords: Insect; Memory; Protein degradation; Ubiquitin proteasome system