Neurotransmitter release regulated by a MALS-liprin-α presynaptic complex

Olav Olsen, Kimberly A. Moore, Masaki Fukata, Toshinari Kazuta, Jonathan C. Trinidad, Fred W. Kauer, Michel Streuli, Hidemi Misawa, Alma L. Burlingame, Roger A. Nicoll, David S. Bredt

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Abstract

Synapses are highly specialized intercellular junctions organized by adhesive and scaffolding molecules that align presynaptic vesicular release with postsynaptic neurotransmitter receptors. The MALS/Veli-CASK-Mint-1 complex of PDZ proteins occurs on both sides of the synapse and has the potential to link transsynaptic adhesion molecules to the cytoskeleton. In this study, we purified the MALS protein complex from brain and found liprin-α as a major component. Liprin proteins organize the presynaptic active zone and regulate neurotransmitter release. Fittingly, mutant mice lacking all three MALS isoforms died perinatally with difficulty breathing and impaired excitatory synaptic transmission. Excitatory postsynaptic currents were dramatically reduced in autaptic cultures from MALS triple knockout mice due to a presynaptic deficit in vesicle cycling. These findings are consistent with a model whereby the MALS-CASK-liprin-α complex recruits components of the synaptic release machinery to adhesive proteins of the active zone.

Original languageEnglish
Pages (from-to)1127-1134
Number of pages8
JournalJournal of Cell Biology
Volume170
Issue number7
DOIs
Publication statusPublished - 2005 Sep 26

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ASJC Scopus subject areas

  • Cell Biology

Cite this

Olsen, O., Moore, K. A., Fukata, M., Kazuta, T., Trinidad, J. C., Kauer, F. W., Streuli, M., Misawa, H., Burlingame, A. L., Nicoll, R. A., & Bredt, D. S. (2005). Neurotransmitter release regulated by a MALS-liprin-α presynaptic complex. Journal of Cell Biology, 170(7), 1127-1134. https://doi.org/10.1083/jcb.200503011