Ecto-protein kinases on the surface of mouse hippocampal pyramidal neurons: Role in neuronal plasticity.
Item
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Title
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Ecto-protein kinases on the surface of mouse hippocampal pyramidal neurons: Role in neuronal plasticity.
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Identifier
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AAI9732899
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identifier
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9732899
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Creator
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Chen, Wei.
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Contributor
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Adviser: Yigal H. Ehrlich
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Date
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1997
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Neuroscience
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Abstract
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The conditions for culturing nearly-pure populations of pyramidal neurons from mouse hippocampus that can be maintained for more than 3 weeks in modified culture conditions and undergo neuritogenesis and synaptogenesis have been established. Ecto-protein kinase activity was identified on the surface of hippocampal primary neurons; a 48K/50K protein duplex was the main endogenous substrates of ecto-protein kinase activity on mature hippocampal pyramidal neurons. The phosphorylation of this duplex by ecto-protein kinase was detected after the initiation of synaptogenesis, but not in immature neurons nor in glial cells. The ecto-protein kinase which phosphorylated the 48K/50K had catalytic activity with properties of protein kinase C (PKC). Addition to the extracellular medium of a monoclonal antibody (mAb 1.9) directed to the catalytic domain of protein kinase C selectively inhibited the phosphorylation of the 48K/50K protein duplex by ecto-protein kinase and blocked the stabilization of long-term potentiation (LTP) induced by high frequency stimulation (HFS) in mouse hippocampal slices. The observation that the phosphorylation of the 48K/50K protein duplex by ecto-protein kinase was developmentally regulated suggests that extracellular phosphorylation of this surface protein duplex may provide a signal for triggering the formation of synapses during neuronal development, and during the maintenance phase of LTP in adult brain. Neuronal development is activity dependent, mostly through N-methyl-D-aspartate (NMDA) receptors, and the activation of NMDA receptors is an initial step in the maintenance of LTP. The evidence presented here that the NMDA receptor may be associated with the phosphorylation of this duplex by ecto-protein kinase further suggests that the phosphorylation of the 48K/50K duplex by ecto-protein kinase may be involved in neuronal development and in the maintenance of LTP. The 50K protein that serves as an endogenous substrate of ecto-protein kinase was found to be related to the intracellular neuronal plasticity protein GAP-43 in molecular mobility and antigenic properties. These results provide the first direct evidence of a causal role for ecto-PK in the maintenance of stable LTP, an event implicated in the process of learning and formation of memory in the brain.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
