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Publication : Neurotransmitter release regulated by a MALS-liprin-alpha presynaptic complex.

First Author  Olsen O Year  2005
Journal  J Cell Biol Volume  170
Issue  7 Pages  1127-34
PubMed ID  16186258 Mgi Jnum  J:102649
Mgi Id  MGI:3607873 Doi  10.1083/jcb.200503011
Citation  Olsen O, et al. (2005) Neurotransmitter release regulated by a MALS-liprin-alpha presynaptic complex. J Cell Biol 170(7):1127-34
abstractText  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-alpha 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-alpha complex recruits components of the synaptic release machinery to adhesive proteins of the active zone.
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