Organization of the presynaptic active zone by ERC2/CAST1-dependent clustering of the tandem PDZ protein syntenin-1.
Presynaptic active zones contain a cytoskeletal matrix called the CAZ, which is thought to play a critical role in the regulation of active zone formation and neurotransmitter release. Recent studies have identified several CAZ components, but little is known about how they contribute to the molecular organization of active zones. Here, we report a novel PDZ [postsynaptic density-95/Discs large/zona occludens-1] interaction between the CAZ protein ERC2/CAST1 and the tandem PDZ protein syntenin-1, which is known to associate with diverse synaptic proteins, including glutamate receptor subunits, SynCAM, and beta-neurexin. This interaction promotes the localization of syntenin-1 at presynaptic ERC2 clusters. In addition to the PDZ interaction, multimerization of both ERC2 and syntenin-1 mediates syntenin-1 clustering. These results suggest that ERC2 promotes presynaptic syntenin-1 clustering by two distinct mechanisms and that syntenin-1 may contribute to the molecular organization of active zones by linking ERC2 and other CAZ components to diverse syntenin-1-associated synaptic proteins.
Ko
Jaewon
J
National Creative Research Initiative Center for Synaptogenesis, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Yoon
Chan
C
Piccoli
Giovanni
G
Chung
Hye Sun
HS
Kim
Karam
K
Lee
Jae-Ran
JR
Lee
Hyun Woo
HW
Kim
Hyun
H
Sala
Carlo
C
Kim
Eunjoon
E
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D053676:Syntenins
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C479908:ERC2 protein, rat; D009419:Nerve Tissue Proteins; C492863:Sdcbp protein, rat; D053676:Syntenins; C033652:postsynaptic density proteins