Abstract
Rap1 is a small GTP-binding protein that has been implicated in intracellular signaling and cytoskeletal control. Here, we show that Rap1 is expressed in rat cortical neurons and plays a critical role in dendritic development. Inhibition of Rap1 signaling either by expressing dominant negative mutant of Rap1 or Rap1GAP in cortical neurons reduced dendritic complexity. In contrast, expression of a constitutively active mutant of Rap1 (Rap1V12) induced dendritic growth and branching. Membrane depolarization, which induces dendritic growth via calcium influx, led to a rapid activation of Rap1 via cAMP and cGMP signaling. A CREB-dependent mechanism is involved in depolarization-induced dendritic growth in cortical neurons. Rap1 function contributed to depolarization induced CREB activation, and inhibition of CREB suppressed dendritic growth induced by Rap1V12. These observations identify Rap1 as a key mediator of calcium regulation of CREB-dependent transcription and dendritic development.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Animals, Newborn
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Calcium Channels / metabolism
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Calcium Signaling / physiology
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Cell Differentiation / genetics*
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Cells, Cultured
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Cerebral Cortex / cytology
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Cerebral Cortex / embryology*
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Cerebral Cortex / growth & development*
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Cyclic AMP / metabolism
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Cyclic AMP Response Element-Binding Protein / metabolism
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Cyclic GMP / metabolism
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Dendrites / metabolism
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Dendrites / physiology*
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Dendrites / ultrastructure
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Gene Expression Regulation, Developmental / genetics*
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Membrane Potentials / physiology
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Mitogen-Activated Protein Kinase 3 / metabolism
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Mutation / genetics
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Rats
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Rats, Long-Evans
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Receptors, N-Methyl-D-Aspartate / metabolism
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Second Messenger Systems / physiology
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Signal Transduction / genetics
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rap1 GTP-Binding Proteins / genetics
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rap1 GTP-Binding Proteins / metabolism*
Substances
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Calcium Channels
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Cyclic AMP Response Element-Binding Protein
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Receptors, N-Methyl-D-Aspartate
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Cyclic AMP
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Mitogen-Activated Protein Kinase 3
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rap1 GTP-Binding Proteins
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Cyclic GMP