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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.


Yachi Chen, Phyllis Y Wang, Anirvan Ghosh. Regulation of cortical dendrite development by Rap1 signaling. Molecular and cellular neurosciences. 2005 Feb;28(2):215-28

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PMID: 15691704

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