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The Journal of Neuroscience, January 18, 2006, 26(3):963-970; doi:10.1523/JNEUROSCI.4475-05.2006

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Cellular/Molecular
Organization of the Presynaptic Active Zone by ERC2/CAST1-Dependent Clustering of the Tandem PDZ Protein Syntenin-1

Jaewon Ko,¹ Chan Yoon,¹ Giovanni Piccoli,² Hye Sun Chung,³ Karam Kim,¹ Jae-Ran Lee,¹ Hyun Woo Lee,¹ Hyun Kim,³ Carlo Sala,² and Eunjoon Kim¹

¹National Creative Research Initiative Center for Synaptogenesis and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea, ²Consiglio Nazionale delle Ricerche, Institute of Neuroscience, Cellular and Molecular Pharmacology, Department of Pharmacology, University of Milan, 20129 Milan, Italy, and ³Department of Anatomy and Division of Brain Korea 21 Biomedical Science, College of Medicine, Korea University, Seoul 136-705, Korea

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 -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.

Key words: ERC; CAST; syntenin; PDZ; multimerization; presynaptic regulation

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Received June 9, 2005; revised November 22, 2005; accepted November 23, 2005.

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