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News tips from the Journal of Neuroscience

1. Ret Signaling and Lipid Rafts
Brian A. Pierchala, Jeffrey Milbrandt, and Eugene M. Johnson Jr.

Pierchala et al. this week followed the plight of the receptor tyrosine kinase (RTK) Ret after its activation. Ret is activated by a complex consisting of a member of the glial cell line-derived neurotrophic factor (GDNF) family and a glycerophosphatidylinositol (GPI)-linked coreceptor. The GPI linkage results in recruitment of Ret into lipid rafts, where its activity is maximal. The authors report that, once activated, Ret disappeared from rat sympathetic neurons over several hours. Some Ret was monoubiquitinated and targeted to the lysosome, but a more substantial fraction was polyubiquitinated and thus sent to proteasomes for degradation. Ret degradation effectively terminated the GDNF-mediated signal. When the authors disrupted lipid rafts, GDNF-mediated neuronal survival was severely diminished, an effect that was reversed by inhibition of proteasomal degradation. Thus, lipid rafts serve to sequester activated Ret and extend its activity.

2. REST in Xenopus Development
Patricio Olgun, Pablo Oteza, Eduardo Gamboa, Jos Luis Gmez-Skrmeta, and Manuel Kukuljan

The transcriptional repressor RE-1 silencer of transcription/neural restrictive silencer factor (REST/NRSF) is best known for its role in silencing neural genes in nonneuronal cells. However, it now appears that REST has more widespread actions in organogenesis and development. This week, Olgun et al. considered its role in vivo during Xenopus laevis development. In embryos, the authors expressed a glucocorticoidinducible dominant-negative construct (dnXREST) that bound to the DNA of target genes but not corepressor proteins. In a second approach, REST translation was blocked by a morpholino antisense oligonucleotide (MoXREST). Activation of dnXREST resulted in decreased expression of several neuronal genes at the late blastula stage. But perha
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Contact: Sara Harris
sharris@sfn.org
202-962-4000
Society for Neuroscience
7-Mar-2006


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