Faculty Collaboration Database

Differential roles of Rap1 and Rap2 small GTPases in neurite retraction and synapse elimination in hippocampal spiny neurons. J Neurochem 2007 Jan;100(1):118-31

Date

01/18/2007

Pubmed ID

17227435

DOI

10.1111/j.1471-4159.2006.04195.x

Scopus ID

2-s2.0-33846136109 (requires institutional sign-in at Scopus site)   71 Citations

Abstract

The Rap family of small GTPases is implicated in the mechanisms of synaptic plasticity, particularly synaptic depression. Here we studied the role of Rap in neuronal morphogenesis and synaptic transmission in cultured neurons. Constitutively active Rap2 expressed in hippocampal pyramidal neurons caused decreased length and complexity of both axonal and dendritic branches. In addition, Rap2 caused loss of dendritic spines and spiny synapses, and an increase in filopodia-like protrusions and shaft synapses. These Rap2 morphological effects were absent in aspiny interneurons. In contrast, constitutively active Rap1 had no significant effect on axon or dendrite morphology. Dominant-negative Rap mutants increased dendrite length, indicating that endogenous Rap restrains dendritic outgrowth. The amplitude and frequency of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-mediated miniature excitatory postsynaptic currents (mEPSCs) decreased in hippocampal neurons transfected with active Rap1 or Rap2, associated with reduced surface and total levels of AMPA receptor subunit GluR2. Finally, increasing synaptic activity with GABA(A) receptor antagonists counteracted Rap2's inhibitory effect on dendrite growth, and masked the effects of Rap1 and Rap2 on AMPA-mediated mEPSCs. Rap1 and Rap2 thus have overlapping but distinct actions that potentially link the inhibition of synaptic transmission with the retraction of axons and dendrites.

Author List

Fu Z, Lee SH, Simonetta A, Hansen J, Sheng M, Pak DT

Author

Sang H. Lee PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Action Potentials
Animals
Animals, Newborn
Cell Differentiation
Cells, Cultured
Diagnostic Imaging
Disks Large Homolog 4 Protein
Embryo, Mammalian
Glutamate Decarboxylase
Green Fluorescent Proteins
Hippocampus
Immunohistochemistry
Intracellular Signaling Peptides and Proteins
Membrane Proteins
Mutagenesis
Neurites
Neurons
Patch-Clamp Techniques
Rats
Rats, Sprague-Dawley
Receptors, AMPA
Synapses
Synaptic Transmission
Time Factors
Transfection
rap GTP-Binding Proteins