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© The Rockefeller University Press, 0021-9525/2003/7/169 $5.00
The Journal of Cell Biology, Volume 162, Number 2, 169-169

Sticky transmission

Axonal transmission dies away as more neurexins are removed (left to right). Missler/Macmillan

Nerve cells restrict neurotransmitter release to their synapses. That restriction, say Markus Missler (Georg-August Universität, Göttingen, Germany), Thomas Sudhof (University of Texas Southwestern, Dallas, TX), and colleagues, is provided in part by the synaptic proteins -neurexins. These cell adhesion proteins promote calcium channel activity, and thus fusion of neurotransmitter vesicles, at the synaptic junctions.

The polymorphism and adhesion properties of neurexins led researchers to suspect a synapse-forming function. But Missler and coworkers found that mice lacking all three -neurexins had ultrastructurally normal synapses. The mice breathed with difficulty and died on the first day after birth. In the brain stem, where breathing rhythms are generated, synapses showed reduced frequency of spontaneous transmission— a possible sign of presynaptic problems. Reduced amplitudes of synaptic responses were also evident after stimulation of neurons in the neocortex.

The reduced transmission was not further reduced by drugs blocking N-type calcium channels, suggesting that neurexins normally help the channels to function. Channels were still made and transported to the cell membrane. Thus, channels may no longer be localized to the synapse or, as Missler suggests, no longer get activated. Consistent with the latter idea, whole cell calcium currents from the cell bodies were also reduced in mutants.

According to the activation hypothesis, "in neurons, unlike in other tissues, a negative clamp may exist on the function of calcium channels, and neurexin is needed to remove this clamp," says Missler. "It may sound a bit out of the blue. But neurons have to control the number of active calcium channels very tightly because of the negative consequences of excessive calcium influx. So neurexin may provide a localized activation of calcium channels at synapses."

Reference:

Missler, M., et al. 2003. Nature. 423:939–948.[CrossRef][Medline]

William A. Wells

wellsw{at}rockefeller.edu

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This Article Full Text (PDF, 774K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?