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.
Ko
Jaewon
J
National Creative Research Initiative Center for Synaptogenesis and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Na
Moonseok
M
Kim
Seho
S
Lee
Jae-Ran
JR
Kim
Eunjoon
E
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001923:Brain Chemistry; D002352:Carrier Proteins / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D004622:Embryo, Mammalian; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D000090204:Mesothelin; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011518:Proto-Oncogene Proteins; D051381:Rats; D013569:Synapses / Q000737:chemistry; D020798:Two-Hybrid System Techniques
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C468925:ERC1 protein, human; C479909:ERC1 protein, rat; C406485:ERC2 protein, human; C479908:ERC2 protein, rat; C000715529:Msln protein, rat; D009419:Nerve Tissue Proteins; C094398:PPFIA1 protein, human; D010750:Phosphoproteins; C490599:Ppfia4 protein, rat; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D000090204:Mesothelin