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
| Autor: | Danay Baker-Andresen, Wayne S. Sossin, Carole A. Farah, Katrina Gong, Tyler W. Dunn, Margaret H. Hastings |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Nervous system Serotonin Microinjections Sensory Receptor Cells Cognitive Neuroscience Presynaptic Terminals Nervous System Membrane Potentials Potassium Chloride 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine immune system diseases Transduction Genetic Aplysia Fluorescence Resonance Energy Transfer medicine Animals Protein Isoforms Enzyme Inhibitors neoplasms Cells Cultured Protein Kinase C Protein kinase C Benzophenanthridines Motor Neurons Neuronal Plasticity biology Calpain Chemistry Research PKCS Motor neuron biology.organism_classification Sensory neuron 030104 developmental biology Neuropsychology and Physiological Psychology medicine.anatomical_structure Gene Expression Regulation Synaptic plasticity biology.protein Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Learning & Memory. 24:1-13 |
| ISSN: | 1549-5485 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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