title: A PKM generated by calpain cleavage of a classical PKC is required for activity-dependent intermediate-term facilitation in the presynaptic sensory neuron of Aplysia.
abstract: Atypical PKM, a persistently active form of atypical PKC, is proposed to be a molecular memory trace, but there have been few examinations of the role of PKMs generated from other PKCs. We demonstrate that inhibitors used to inhibit PKMs generated from atypical PKCs are also effective inhibitors of other PKMs. In contrast, we demonstrate that dominant-negative PKMs show isoform-specificity. A dominant-negative PKM from the classical PKC Apl I blocks activity-dependent intermediate-term facilitation (a-ITF) when expressed in the sensory neuron, while a dominant-negative PKM from the atypical PKC Apl III does not. Consistent with a specific role for PKM Apl I in activity-dependent facilitation, live imaging FRET-based cleavage assays reveal that activity leads to cleavage of the classical PKC Apl I, but not the atypical PKC Apl III in the sensory neuron varicosities of Aplysia In contrast, massed intermediate facilitation (m-ITF) induced by 10 min of 5HT is sufficient for cleavage of the atypical PKC Apl III in the motor neuron. Interestingly, both cleavage of PKC Apl I in the sensory neuron during a-ITF and cleavage of PKC Apl III in the motor neuron during m-ITF are inhibited by a dominant-negative form of a penta-EF hand containing classical calpain cloned from Aplysia Consistent with a role for PKMs in plasticity, this dominant-negative calpain also blocks both a-ITF when expressed in the sensory neuron and m-ITF when expressed in the motor neuron. This study broadens the role of PKMs in synaptic plasticity in two significant ways: (i) PKMs generated from multiple isoforms of PKC, including classical isoforms, maintain memory traces; (ii) PKMs play roles in the presynaptic neuron.
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Carole A
authors.initials: CA
authors.lastname: Farah
authors.affiliation: Department of Psychology, McGill University, Montreal Neurological Institute, Montreal, Quebec H3A 1B1, Canada.
authors.forename: Margaret H
authors.initials: MH
authors.lastname: Hastings
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Tyler W
authors.initials: TW
authors.lastname: Dunn
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Katrina
authors.initials: K
authors.lastname: Gong
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Danay
authors.initials: D
authors.lastname: Baker-Andresen
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada wayne.sossin@mcgill.ca.|Department of Psychology, McGill University, Montreal Neurological Institute, Montreal, Quebec H3A 1B1, Canada.
authors.forename: Wayne S
authors.initials: WS
authors.lastname: Sossin
mesh_terms: D000818:Animals; D001048:Aplysia; D053119:Benzophenanthridines / Q000494:pharmacology; D002154:Calpain / Q000494:pharmacology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D031541:Fluorescence Resonance Energy Transfer; D005786:Gene Expression Regulation / Q000187:drug effects; D008564:Membrane Potentials / Q000502:physiology; D008845:Microinjections; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009420:Nervous System / Q000166:cytology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000166:cytology* / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D014161:Transduction, Genetic
chemical_list: D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D020033:Protein Isoforms; D012701:Serotonin; D011189:Potassium Chloride; C016299:chelerythrine; D011493:Protein Kinase C; D002154:Calpain