Catenin keeps vesicles close

Synapse creation and maintenance takes more than the transport of proteins to the correct site, according to Shernaz Bamji, Louis Reichardt (University of California, San Francisco, CA), and colleagues. They find that synaptic vesicles are kept localized, ready for action on the presynaptic side, thanks to a PDZ-binding domain on β-catenin. The β-catenin is localized by cadherin adhesion proteins, thus linking axon–dendrite adhesion to the localization of presynaptic vesicles.

Loss of β-catenin is not exactly disastrous. Mice with β-catenin deleted from hippocampal neurons after synapse formation showed normal levels of docked neurotransmitter vesicles, and broadly similar short-term responses to stimulation. But, in the mutants, nondocked vesicles were not as well localized at the site of action, so prolonged stimulation led to a faster drop-off in transmission. Similar results were seen in vitro after expression of a β-catenin lacking its PDZ-binding domain.

With β-catenin functioning as a scaffold, “it's not clear to me how much adhesion you need as opposed to signaling,” says Reichardt. “Cadherins do nucleate this diversity of signaling pathways. Whether you need contact [between axon and dendrite] because that nucleates something or contact because that puts you into position [for signaling] is not known.” ▪

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