Regulation of Cortical Dendrite Development by Rap1 Signaling

Mol Cell Neurosci. 2005 Feb;28(2):215-28. doi: 10.1016/j.mcn.2004.08.012.

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

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Calcium Channels / metabolism
  • Calcium Signaling / physiology
  • Cell Differentiation / genetics*
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / embryology*
  • Cerebral Cortex / growth & development*
  • Cyclic AMP / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Cyclic GMP / metabolism
  • Dendrites / metabolism
  • Dendrites / physiology*
  • Dendrites / ultrastructure
  • Gene Expression Regulation, Developmental / genetics*
  • Membrane Potentials / physiology
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Mutation / genetics
  • Rats
  • Rats, Long-Evans
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Second Messenger Systems / physiology
  • Signal Transduction / genetics
  • rap1 GTP-Binding Proteins / genetics
  • rap1 GTP-Binding Proteins / metabolism*

Substances

  • Calcium Channels
  • Cyclic AMP Response Element-Binding Protein
  • Receptors, N-Methyl-D-Aspartate
  • Cyclic AMP
  • Mitogen-Activated Protein Kinase 3
  • rap1 GTP-Binding Proteins
  • Cyclic GMP