Regulation of cortical dendrite development by Rap1 signaling
Copyright policy )Regulation of cortical dendrite development by Rap1 signaling
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.
- Johns Hopkins Medicine United States
- Johns Hopkins University School of Medicine United States
- University of California, San Diego United States
Cerebral Cortex, Mitogen-Activated Protein Kinase 3, Gene Expression Regulation, Developmental, Cell Differentiation, Dendrites, Receptors, N-Methyl-D-Aspartate, Second Messenger Systems, Membrane Potentials, Rats, Animals, Newborn, Mutation, Cyclic AMP, Animals, Rats, Long-Evans, Calcium Channels, Calcium Signaling, Cyclic AMP Response Element-Binding Protein, Cyclic GMP, Cells, Cultured, Signal Transduction
Cerebral Cortex, Mitogen-Activated Protein Kinase 3, Gene Expression Regulation, Developmental, Cell Differentiation, Dendrites, Receptors, N-Methyl-D-Aspartate, Second Messenger Systems, Membrane Potentials, Rats, Animals, Newborn, Mutation, Cyclic AMP, Animals, Rats, Long-Evans, Calcium Channels, Calcium Signaling, Cyclic AMP Response Element-Binding Protein, Cyclic GMP, Cells, Cultured, Signal Transduction
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