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The Journal of Neuroscience, February 16, 2005, 25(7)
This Week in The Journal
Cellular/Molecular
FRETing Glutamate Transporters
Hans P. Koch and H. Peter Larsson
(see pages 1730-1736)
This week, Koch and Larsson report that the glutamate transporter known as excitatory amino acid transporter 3 (EAAT3) seems to do its work without a lot of motion. The authors used fluorescence resonance energy transfer (FRET), in which energy transfers from donor to acceptor fluorophores, to map intramolecular distances. Cysteine mutations were used to tag various pairs of sites with cysteine-reactive fluorescent probes. The large calculated distances for intersubunit sites in the extracellular domain suggested that EAAT3 is likely trimeric rather than pentameric, with a "doughnut-shaped" large extracellular vestibule. Unlike other transporters, the FRET measurements predict that only small (<5 Å) conformational changes accompany the transport cycle. Buttressed by a recently published structure of a bacterial glutamate transporter by Yernool et al. (2004), the authors suggest that the large extracellular vestibule is connected to the cytoplasm by a short channel. Thus glutamate transport may not require the large conformation movements of the so-called rocker-switch model that has been suggested for some transporters.
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Alternative models of transporters. The rocker-switch model involves large conformational movements of subunits (a), whereas the channel model has two gates that open alternatively, allowing coupled transport (b). See the article by Koch and Larsson for details.
Development/Plasticity/Repair
A STAT3 Call for Regeneration
Jin Qiu, William B. J. Cafferty, Stephen B. McMahon, and Stephen W. N. Thompson
(see pages 1645-1653)
Regeneration in the CNS after spinal cord injury is limited because of obstacles such as glial scars and myelin-based inhibitory factors. On the other hand, axons in the PNS are much more resilient. Dorsal root ganglion (DRG) neurons provide a striking example of this dichotomy, because their peripheral axon branches regenerate but their central branches do not. However, transection of peripheral DRG axon branches, a "conditioning" injury, actually promotes regeneration of the central axons, possibly by upregulation of the cytokines leukemia inhibitory factor and interleukin-6. This week, Qiu et al. provide evidence for Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling downstream of the cytokines. After peripheral nerve transection, there was enhanced phosphorylation of the transcription factor STAT3 in DRG neurons, whereas the JAK2 kinase inhibitor AG490 reduced the injury-induced regeneration of central processes. Thus the JAK2-STAT3 pathway appears to be growth-promoting after a peripheral nerve injury.
Behavioral/Systems/Cognitive
Cell Adaptation and Area 17 Receptive Fields
Lionel G. Nowak, Maria V. SanchezVives, and David A. McCormick
(see pages 1866-1880)
Receptive fields (RFs) of neurons in the visual cortex define the area in the visual field where stimuli evoke changes in action potential firing patterns. Although such discharge RFs can be precisely mapped, they also are dynamic in both space and time. For example, RFs are larger for low-contrast stimuli. Nowak et al. examined some of the cellular mechanisms in cat primary visual cortex neurons that might contribute to the dynamics of RFs. High-contrast stimuli reduced the strength of firing in the RF and also reduced its width. These changes were accompanied by membrane hyperpolarization. Likewise, current injections that produced hyperpolarization mimicked the effects of high-contrast stimuli. The gain and width of the discharge RF increased after adaptation to visual surround stimulation (an "artificial scotoma") or unpatterned stimulation ("gray screen"). The authors conclude that the membrane and synaptic properties of the area 17 neurons contribute to dynamic changes in RF.
Neurobiology of Disease
A Mouse Model of Guillain-Barré Syndrome
John A. Goodfellow, Tyrone Bowes, Kazim Sheikh, Masaaki Odaka, Susan K. Halstead, Peter D. Humphreys, Eric R. Wagner, Nobuhiro Yuki, Koichi Furukawa, Keiko Furukawa, Jaap J. Plomp, and Hugh J. Willison
(see pages 1620-1628)
Although the acute muscle paralysis that accompanies Guillain-Barré syndrome (GBS) is usually self-limited, its presentation can be dramatic and life-threatening. GBS is an autoimmune disorder that is usually preceded by a viral or bacterial illness. Gastroenteritis caused by Campylobacter jejuni is now recognized as a frequent cause of GBS, particularly in Japan and China. The acute motor axonal form of GBS is accompanied by circulating antibodies to the ganglioside GD1a. Interestingly, C. jejuni express GD1a-like antigens on their surface lipo-oligosaccharide. To examine whether circulating GD1a antibodies cause the disease, Goodfellow et al. generated anti-GD1a antibodies in GD1a-deficient mice inoculated with the bacterial protein. They then applied the purified antibodies to nerve terminals in an ex vivo preparation. The antibodies and their complement targeted and damaged neuromuscular junctions in GD1a-overexpressing mice but not in normal mice. Their results support molecular mimicry as the culprit in this disorder but also indicate the importance of membrane antigen density in the antibody-mediated damage.
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