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The Journal of Neuroscience, December 31, 2008, 28(53):14546-14556; doi:10.1523/JNEUROSCI.3112-08.2008

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 Previous Article

Cellular/Molecular
Preso, A Novel PSD-95-Interacting FERM and PDZ Domain Protein That Regulates Dendritic Spine Morphogenesis

Hyun Woo Lee,¹ Jeonghoon Choi,¹ Hyewon Shin,¹ Karam Kim,¹ Jinhee Yang,¹ Moonseok Na,¹ So Yoen Choi,² Gil Bu Kang,³ Soo Hyun Eom,³ Hyun Kim,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, ²Department of Anatomy and Division of Brain Korea 21 Biomedical Science, College of Medicine, Korea University, Seongbuk-Gu, Seoul 136-705, Korea, and ³Department of Life Science, Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea

Correspondence should be addressed to Eunjoon Kim, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Kuseong-dong, Yuseong-ku, Daejeon 205-701, Korea. Email: kime{at}kaist.ac.kr

PSD-95 is an abundant postsynaptic density (PSD) protein involved in the formation and regulation of excitatory synapses and dendritic spines, but the underlying mechanisms are not comprehensively understood. Here we report a novel PSD-95-interacting protein Preso that regulates spine morphogenesis. Preso is mainly expressed in the brain and contains WW (domain with two conserved Trp residues), PDZ (PSD-95/Dlg/ZO-1), FERM (4.1, ezrin, radixin, and moesin), and C-terminal PDZ-binding domains. These domains associate with actin filaments, the Rac1/Cdc42 guanine nucleotide exchange factor βPix, phosphatidylinositol-4,5-bisphosphate, and the postsynaptic scaffolding protein PSD-95, respectively. Preso overexpression increases the density of dendritic spines in a manner requiring WW, PDZ, FERM, and PDZ-binding domains. Conversely, knockdown or dominant-negative inhibition of Preso decreases spine density, excitatory synaptic transmission, and the spine level of filamentous actin. These results suggest that Preso positively regulates spine density through its interaction with the synaptic plasma membrane, actin filaments, PSD-95, and the βPix-based Rac1 signaling pathway.

Key words: PSD-95; WW; PDZ; FERM; actin; spine

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Received July 4, 2008; revised Oct. 30, 2008; accepted Nov. 23, 2008.

Correspondence should be addressed to Eunjoon Kim, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Kuseong-dong, Yuseong-ku, Daejeon 205-701, Korea. Email: kime{at}kaist.ac.kr

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