Article

The novel GTPase Rit differentially regulates axonal and dendritic growth.

Center for Research on Occupational and Environmental Toxicology, Oregon Health & Science University, Portland, Oregon 97239, USA.
Journal of Neuroscience (impact factor: 7.11). 05/2007; 27(17):4725-36. DOI:10.1523/JNEUROSCI.5633-06.2007 pp.4725-36
Source: PubMed

ABSTRACT The Rit GTPase is widely expressed in developing and adult nervous systems, and our previous data with pheochromocytoma cells implicate Rit signaling in NGF-induced neurite outgrowth. In this study, we investigated a role for Rit in neuronal morphogenesis. Expression of a dominant-negative (dn) Rit mutant in hippocampal neurons inhibited axonal growth but potentiated dendritic growth. Conversely, a constitutively active (ca) Rit mutant promoted axonal growth but inhibited dendritic growth. Dendritogenesis is regulated differently in sympathetic neurons versus hippocampal neurons in that sympathetic neurons require NGF and bone morphogenetic proteins (BMPs) to trigger dendritic growth. Despite these differences, dnRit potentiated and caRit blocked BMP7-induced dendritic growth in sympathetic neurons. Biochemical studies indicated that BMP7 treatments that caused dendritic growth also decreased Rit GTP loading. Additional studies demonstrate that caRit increased extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and pharmacological inhibition of MEK1 (mitogen-activated protein kinase/ERK 1) blocked the axon-promoting and dendrite-inhibiting effects of caRit. These observations suggest that Rit is a convergence point for multiple signaling pathways and it functions to promote axonal growth but inhibit dendritic growth via activation of ERK1/2. Modulation of the activational status of Rit may therefore represent a generalized mechanism across divergent neuronal cell types for regulating axonal versus dendritic growth modes.

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Keywords

activational status
 
Additional studies
 
axonal growth
 
Biochemical studies
 
BMP7 treatments
 
BMP7-induced dendritic growth
 
caused dendritic growth
 
dendritic growth
 
dendritic growth modes
 
extracellular signal-regulated kinase 1/2
 
hippocampal neurons
 
hippocampal neurons inhibited axonal growth
 
inhibited dendritic growth
 
multiple signaling pathways
 
neuronal morphogenesis
 
NGF-induced neurite outgrowth
 
potentiated dendritic growth
 
previous data
 
Rit GTP loading
 
sympathetic neurons