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The Journal of Neuroscience, April 7, 2004, 24(14)
This Week in the Journal
Cellular/Molecular
Another Lesson from GluR2
Scott J. Myers, Yunfei Huang, Thomas Genetta, and Raymond Dingledine
(see pages 3489–3499)
The glutamate receptor 2 (GluR2) subunit is sort of the kingpin of AMPA receptor subunits, because its inclusion in this heteromeric assembly controls key aspects of their single-channel properties, including calcium permeability. More than 10 years ago, Seeburg and colleagues reported the remarkable observation that RNA editing of GluR2 in fact controlled these properties. Perhaps consistent with its key function, transcription of GluR2 is also regulated by activity as well as ischemia and seizures. This week, Myers et al. reveal the interesting complexity of GluR2 translational regulation. GluR2 has multiple transcription initiation sites in the 5'-untranslated region that result in different length transcripts, but the authors found that translation was not regulated simply by the site of initiation, but rather by a translation suppression domain consisting of a variable length GU repeat sequence. Transcripts lacking this sequence associated more readily with polyribosomes. The authors suggest that the GU sequence interferes with translation by affecting mRNA secondary structure, and thus could titrate GluR2 levels in neurons.
Development/Plasticity/Repair
For Motor Neurons, It's Death without Rho
Kenta Kobayashi, Masanori Takahashi, Natsuki Matsushita, Jun-ichi Miyazaki, Masato Koike, Hiroyuki Yaginuma, Noriko Osumi, Kozo Kaibuchi, and Kazuto Kobayashi
(see pages 3480–3488)
The small GTPase Rho often mediates intracellular signaling events by activating its downstream partner, Rho-dependent serine threonine kinase (Rho-kinase). In this issue, Kobayashi et al. examined the role of this signaling cascade during early motor neuron development in the mouse spinal cord. They used transgenic mice to conditionally express dominant-negative forms of RhoA or Rho-kinase. Developing motor neurons are subject to programmed cell death (PCD), a process regulated by trophic factors. However, the authors report that Rho signaling is necessary for survival of neurons before the period of PCD. The dominant-negative expression of RhoA or Rho-kinase increased apoptotic death but did not disrupt the patterning of motor neuron axons. Thus Rho signaling appears to be important for cell survival during early development in a manner that is independent of target-derived trophic support.
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Motor neuron apoptosis increased during early development in transgenic mice expressing a dominant-negative form of Rho-kinase. Degenerating motor neurons are TUNEL-positive (gold). See the article by Kobayashi et al. for details.
Behavioral/Systems/Cognitive
Smelling without cAMP Signaling
Weihong Lin, Julie Arellano, Burton Slotnick, and Diego Restrepo
(see pages 3703–3710)
Multiple lines of evidence suggest that odor detection in the main olfactory system involves coupling of cAMP to cyclic nucleotide-gated (CNG) channels in olfactory receptor neurons. However, other odorant transduction mechanisms exist in other species and in the pheromone-mediated vomeronasal system. It has been argued that residual smell in mice lacking CNG channels could be attributed to activation of vomeronasal pathways rather than alternate transduction pathways in the main olfactory bulb (MOB). Lin et al. revisit this question using mice deficient in the CNG channel subunit A2. They used extracellular recording, c-fos imaging, and behavior to assess response to odorants and putative pheromones. Most convincingly, ethyl acetate was detected behaviorally and activated specific glomeruli in the MOB in the mutant mice, an effect that disappeared after olfactory bulb lesions. Although these experiments do not identify the cAMP-independent pathway, they provide a motivation to keep looking for it.
Neurobiology of Disease
Cellular Phenotypes of Diffuse Brain Injury
Richard H. Singleton and John T. Povlishock
(see pages 3543–3553)
Motor-vehicle accidents are a frequent cause of "acceleration–deceleration" brain injuries in which the brain essentially is whiplashed on the brainstem like a ball on a tether. The neurological symptoms are often more serious and diffuse than is apparent on brain imaging, leading to the idea that axon stretch or shearing is the underlying cause. Diffuse axonal and vascular changes have been reported. However, in this issue Singleton and Povlishock use a rat model of traumatic brain injury to show that direct neuronal somatic injury is also present. They infused 10–40 kDa tracers into the ventricles before a fluid percussion injury delivered to the extradural space. The tracers accumulated in widespread neuronal somata and dendrites as soon as 5 min after the injury. Comparison with other markers indicated that somatic injury did not result from adjacent axonal injury and did not inevitably lead to neuronal death. Although the underlying mechanisms are still unknown, these results reveal a more complex pathophysiology for diffuse brain injury than has been assumed previously.
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