Interaction of the ERC family of RIM-binding proteins with the liprin-alpha family of multidomain proteins.

Liprin-alpha/SYD-2 is a family of multidomain proteins with four known isoforms. One of the reported functions of liprin-alpha is to regulate the development of presynaptic active zones, but the underlying mechanism is poorly understood. Here we report that liprin-alpha directly interacts with the ERC (ELKS-Rab6-interacting protein-CAST) family of proteins, members ...
of which are known to bind RIMs, the active zone proteins that regulate neurotransmitter release. In vitro results indicate that ERC2/CAST, an active zone-specific isoform, interacts with all of the known isoforms of liprin-alpha and that liprin-alpha1 associates with both ERC2 and ERC1b, a splice variant of ERC1 that distributes to both cytosolic and active zone regions. ERC2 colocalizes with liprin-alpha1 in cultured neurons and forms a complex with liprin-alpha1 in brain. Liprin-alpha1, when expressed alone in cultured neurons, shows a partial synaptic localization. When coexpressed with ERC2, however, liprin-alpha1 is redistributed to synaptic sites. Moreover, roughly the first half of ERC2, which contains the liprin-alpha-binding region, is sufficient for the synaptic localization of liprin-alpha1 while the second half is not. These results suggest that the interaction between ERC2 and liprin-alpha may be involved in the presynaptic localization of liprin-alpha and the molecular organization of presynaptic active zones.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Brain Chemistry, Carrier Proteins, Embryo, Mammalian, Hippocampus, Humans, Microscopy, Fluorescence, Nerve Tissue Proteins, Neurons, Phosphoproteins, Protein Binding, Protein Isoforms, Protein Structure, Tertiary, Protein Transport, Proto-Oncogene Proteins, Rats, Synapses, Two-Hybrid System Techniques
J. Biol. Chem.
Date: Oct. 24, 2003
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