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doi: 10.1242/10.1242/jcs.00127

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The postsynaptic density and dendritic raft localization of PSD-Zip70, which contains an N-myristoylation sequence and leucine-zipper motifs

¹ Department of Neuroscience (D13), 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
² Ophthalmology (E7) Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
³ Department of Pharmacology, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan
⁴ Department of Neuroplasticity, Research Center on Aging and Adaptation, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan
⁵ Department of Neuroanatomy, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka 020-8505, Japan

^* Author for correspondence (e-mail: sobue{at}nbiochem.med.osaka-u.ac.jp)

Accepted 28 August 2002

The postsynaptic site of the excitatory synapse, which is composed of the postsynaptic density (PSD) attached to the postsynaptic membrane, is a center for synaptic plasticity. To reveal the molecular organization and functional regulation of the postsynaptic site, we cloned a 70 kDa protein that is concentrated in PSDs using a monoclonal antibody against the PSD. This protein, named PSD-Zip70, is highly homologous to the human FEZ1/LZTS1 gene product. PSD-Zip70 contains an N-myristoylation consensus sequence, a polybasic cluster in the N-terminal region and four leucine-zipper motifs in the C-terminal region. Light and electron microscopy showed that this protein was localized to the dendritic spines, especially in the PSD and the postsynaptic membrane. Fractionation of the synaptic plasma membrane demonstrated that PSD-Zip70 was localized to the PSD and the dendritic raft. In Madin-Darby canine kidney (MDCK) cells, exogenous PSD-Zip70 was targeted to the apical plasma membrane of microvilli, and its N-myristoylation was necessary for this targeting. In hippocampal neurons, N-myristoylation was also required for the membrane localization and the C-terminal region was critically involved in the synaptic targeting. These results suggest that PSD-Zip70 may be involved in the dynamic properties of the structure and function of the postsynaptic site.

Key words: Postsynaptic density, PSD, Dendritic raft, Microvilli, Hippocampus, Myristoylation, Leucine-zipper

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