Synamon, a Novel Neuronal Protein Interacting with Synapse-associated Protein 90/Postsynaptic Density-95-associated Protein

doi:10.1074/jbc.274.39.27463

Synamon, a Novel Neuronal Protein Interacting with Synapse-associated Protein 90/Postsynaptic Density-95-associated Protein*

From the ^‡Takai Biotimer Project, Exploratory Research for Advanced Technology, Japan Science and Technology Corporation, c/o JCR Pharmaceuticals Co. Ltd., 2-2-10 Murotani, Nishi-ku, Kobe 651-2241, Japan and ^§Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine, Faculty of Medicine, Suita 565-0871, Japan

Abstract

Guanylate kinase-associated protein (GKAP)/SAP90/PSD-95-associated protein (SAPAP)/DLG-associated protein (DAP) is a protein of the postsynaptic density (PSD), and binds to the guanylate kinase domain of PSD-95/synapse-associated protein (SAP) 90 and synaptic scaffolding molecule. GKAP/SAPAP/DAP recruits PSD-95/SAP90 and its interacting protein, brain-enriched guanylate kinase-interacting protein, into the Triton X-100-insoluble fraction in transfected cells, suggesting that GKAP/SAPAP/DAP may link several PSD components to the Triton X-100-insoluble structures in the PSD. We have identified here a novel neuronal GKAP/SAPAP/DAP-binding protein and named it synamon. Synamon has seven ankyrin repeats at the NH₂ terminus followed by one src homology 3 domain and one PSD-95/Dlg-A/ZO-1 domain, and several proline-rich regions at the carboxyl terminus. Synamon interacts with the COOH-terminal region of GKAP/SAPAP/DAP via the middle region containing a PSD-95/Dlg-A/ZO-1 domain. Synamon was coimmunoprecipitated with SAPAP from rat crude synaptosomes and colocalized with SAPAP in primary cultured rat hippocampal neurons. Because synamon is composed of various protein-interacting modules, it may also interact with proteins other than GKAP/SAPAP/DAP to organize the architecture of the PSD.

Footnotes

↵* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) .
↵¶ To whom correspondence should be addressed. Tel: 81-6-6879-3410; Fax: 81-6-6879-3419; E-mail: ytakai@molbio.med.osak-u.ac.jp.
Abbreviations:

PSD

postsynaptic density

SAP90

synapse-associated protein 90

GKAP

guanylate kinase-associated protein

SAPAP

SAP90/PSD-95-associated protein

DAP

DLG-associated protein

BEGAIN

brain-enriched guanylate kinase-interacting protein

S-SCAM

synaptic scaffolding molecule

aa

amino acid

SH3

src homology 3

NMDA

N-methyl-d-aspartate

GST

glutathioneS-transferase
- Received February 8, 1999.
- Revision received May 21, 1999.
The American Society for Biochemistry and Molecular Biology, Inc.