Physics. Cooking a two-dimensional electron gas with microwaves.
نویسندگان
چکیده
O ne would think that a mouse lacking the major excitatory neurotransmit-ter in the brain would be a dead mouse, and indeed it is—but it's not nearly as dead as one might have thought. Two groups have knocked out the gene for the main vesicular glutamate transporter, VGLUT1, and surprisingly, these mice live for several months. The studies by Fremeau et al. (1) on page 1815 in this issue and by Wojcik et al. in a recent issue of Proceedings of the National Academy of Sciences U.S.A. (2) both look at transporter expression, trafficking , and mechanisms of vesicle loading in VGLUT1 mutant mice. However, the two studies present different models for subcel-lular localization of the vesicular transporter and for vesicle loading. Neurotransmitters are stored in synaptic vesicles at neuron terminals that contact other neurons. When the synaptic vesicle membrane fuses with the plasma membrane, the neurotransmitter is released into the synaptic cleft. The main excitatory neurotransmitter in the brain is the amino acid glutamate. It was recently found that the vesicular gluta-mate transporter, which had eluded researchers for many years, was actually disguised as a plasma membrane inorganic phosphate transporter (3–6). This transporter was named VGLUT1 and two additional glutamate transporters—VGLUT2 and VGLUT3—have since been identified (7–11). Deleting the gene for the vesicular glutamate transporter would prevent release of glutamate into the synaptic cleft, which could reveal the function of this neurotrans-mitter. The Fremeau et al. (1) and Wojcik et al. (2) studies both show that excitatory neu-rotransmission is greatly reduced in VGLUT1 knockout mice—as expected if neurons were releasing empty vesicles. However, analysis of the small amounts of current remaining lead to different interpretations. Why are there three vesicular glutamate transporters? One possibility is that these transporters have different kinetics for neu-rotransmitter loading. However, the transporters exhibit very similar transport kinet-ics (3, 4, 8–14). A second possibility is that the three transporters are expressed in different parts of the brain. In fact, in adult mice, the distribution of the transporters is mostly nonoverlapping. Roughly, VGLUT1 is expressed in the cortex, VGLUT2 is expressed in the brainstem, and VGLUT3, suprisingly, is expressed in a small number of cells that are not thought to use glutamate as their neurotransmitter (7–9, 12–14). However, Fremeau et al. (1) and Wojcik et al. (2) demonstrate that in newborn mice, both VGLUT1 and VGLUT2 are expressed in the cortex and hippocampus, with VGLUT2 expression …
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ورودعنوان ژورنال:
- Science
دوره 304 5678 شماره
صفحات -
تاریخ انتشار 2004