News Tips From The Journal Of Neuroscience

Main Category: Neurology / Neuroscience
Also Included In: Parkinson's Disease
Article Date: 02 Feb 2007 - 7:00 PDT

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Adding Membranes to Synapses

Nothing is a more fundamental operation than addition, even when it comes to synaptic membranes. This week, Gorczyca et al. addressed the complex process of targeted membrane addition at the larval Drosophila neuromuscular junction, particularly the specialized, multilayered postsynaptic membrane called the subsynaptic reticulum (SSR). The authors used the guanylate kinaselike domain of the fly scaffolding protein Discs-Large (DLG) as bait in a yeast two-hybrid screen. They isolated guanylate kinase-interacting syntaxin [Gtaxin (GTX)]. GTX colocalized with DLG at postsynaptic glutamatergic type I boutons but not at type II and III boutons. GTX and DLG interacted in vivo, and targeting of GTX to the SSR depended on DLG. Like dlg mutants, gtx mutants exhibited a severely compromised SSR. Overexpression of GTX resulted in the formation of extrasynaptic SSR-like structures independent of DLG, indicating a role for GTX in membrane addition.

David Gorczyca, James Ashley, Sean Speese, Norberto Gherbesi, Ulrich Thomas, Eckart Gundelfinger, L. Sian Gramates, and Vivian Budnik

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Drosophila Cacophony Channels

In the second of three papers using Drosophila in This Week in the Journal, Peng and Wu cataloged the diverse properties of calcium channel currents encoded by the cacophony (cac) locus. The authors made whole-cell voltage-clamp and current-clamp recordings from cultured "giant" neurons, generated from fly embryo cells in which cytokinesis had been halted. Recordings from neurons in wildtype and two cac mutants, cacs and cacts2, showed that cac currents varied in their kinetics, displaying low- and high-voltage activation and both fast and slow inactivation. Interestingly, the currents were sensitive to T-type but not L-type calcium channel blockers. Calcium entry through cac-encoded channels was required for calcium-activated potassium current (IK(Ca) ). In cac mutant neurons, the inactivating potassium current IA was upregulated, an effect mimicked by chronic pharmacological block of cac channels, apparently attributable to upregulation of Shaker (Sh) potassium channels.

I-Feng Peng and Chun-Fang Wu

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Roll, Pitch, and Yaw, Lamprey-Style

Steering a lamprey through the murky depths presents some of the same engineering control issues that face airplane pilots. This week, Zelenin et al. examined the control system of the lamprey that maintains body orientation in the sagittal (pitch), transversal (roll), and horizontal (yaw) planes. Brainstem reticulospinal (RS) neurons receive vestibular inputs and send outputs to the motoneuron pools to maintain body orientation. The authors used an in vitro preparation in which the brainstem, vestibular organs, and rostral spinal cord were dissected en bloc along with the cranium and notochord. The notochord was attached to the chamber, and the cranium was attached to a plate that rotated around three axes. The authors made intracellular recordings from RS neurons, and recorded motoneuron responses with surface electrodes. In each plane, RS neurons responded to rotations in one of two opposing directions. Each RS group drove motoneurons that led to a corrective movement.

Pavel V. Zelenin, Grigori N. Orlovsky, and Tatiana G. Deliagina

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A Fly Model of Parkin-Induced PD

Although most cases of Parkinson's disease (PD) are sporadic, mutations in parkin underlie an autosomal recessive juvenile form as well as some adult cases. This week, Sang et al. used a Drosophila model system to test whether parkin mutations and dopamine co-conspire to cause the selective vulnerability of dopaminergic neurons. The authors expressed human wild-type parkin (parkinwt) or familial PD parkin mutants (parkinT240R and parkinQ311X) in fly aminergic neurons under control of a DOPA decarboxylase (ddc)-GAL4 driver. Immediately after eclosion, all flies performed equally well on tests of motor function, but by 4 weeks, flies expressing mutant parkin were severely impaired, and DA neurons were specifically and progressively reduced. Overexpression of the DVMAT(Drosophila vesicular monoamine transporter), which controls cytosolic levels of DA, rescued flies from the mutant parkin phenotype. The idea is that dopamine oxidation leads to modification of parkin, particularly mutant forms, reducing its E3 ligase activity and increasing susceptibility to cell toxicity.

Tzu-Kang Sang, Hui-Yun Chang, George M. Lawless, Anuradha Ratnaparkhi, Lisa Mee, Larry C. Ackerson, Nigel T. Maidment, David E. Krantz, and George R. Jackson

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Contact: Sara Harris
Society for Neuroscience

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