nArgBP2, a Novel Neural Member of Ponsin/ArgBP2/Vinexin Family That Interacts with Synapse-associated Protein 90/Postsynaptic Density-95-associated Protein (SAPAP)

doi:10.1074/jbc.274.43.30914

nArgBP2, a Novel Neural Member of Ponsin/ArgBP2/Vinexin Family That Interacts with Synapse-associated Protein 90/Postsynaptic Density-95-associated Protein (SAPAP)*

From the ^‡Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Japan, the ^§Takai Biotimer Project, ERATO, Japan Science and Technology Corporation, c/o JCR Pharmaceuticals Co. Ltd., Kobe 651-2241, Japan, the ^¶Department of Medical Biochemistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan, and the ^‖Department of Anatomy and Neurobiology, Graduate School, Kyoto University, Kyoto 606-8315, Japan

Abstract

Postsynaptic density (PSD)-95/synapse-associated protein (SAP) 90 and synaptic scaffolding molecule (S-SCAM) are synaptic membrane-associated guanylate kinases. Both the proteins interact with SAP90/PSD-95-associated protein (SAPAP) (also called guanylate kinase-associated protein/Dlg-associated protein). SAPAP is a protein highly enriched in the PSD fraction and may link PSD-95/SAP90 and S-SCAM to Triton X-100-insoluble structures. We found here a novel SAPAP-interacting protein, which was specifically expressed in neural tissue and was present in the postsynaptic density fraction in brain. This protein had a sorbin homology domain in the N terminus, a zinc finger motif in the middle region, and three src homology (SH) 3 domains in the C terminus and was homologous to the ponsin/ArgBP2/vinexin family proteins. We named this protein nArgBP2 because it was the most homologous to ArgBP2. nArgBP2 is a neural member of a growing family of SH3-containing proteins. nArgBP2 bound to the proline-rich region of SAPAP via its third SH3 domain and was coimmunoprecipitated with SAPAP from the extract of rat brain. Furthermore, nArgBP2 was colocalized with SAPAP at synapses in cerebellum. nArgBP2 bound to not only SAPAP but also vinculin and l-afadin, known to bind to ponsin and vinexin. nArgBP2 may be implicated in the protein network around SAPAP in the PSD.

Footnotes

↵* The work performed at Osaka University Graduate School of Medicine/Faculty of Medicine was supported by grants-in-aid for Scientific Research and for Cancer Research from the Ministry of Education, Science, Sports, and Culture, Japan (1998) and by grants from the Human Frontier Science Program (1998).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

SAP

synapse-associated protein

PDZ

PSD-95/Dlg-A/ZO-1

SH

src homology

GK

guanylate kinase

SAPAP

SAP90/PSD-95-associated protein

GKAP

guanylate kinase-associated protein

DAP

hDLG-associated protein

S-SCAM

synaptic scaffolding molecule

NMDA

N-methyl-d-aspartate

MAGUIN

membrane-associated guanylate kinase-interacting protein

BEGAIN

brain-enriched guanylate kinase-interacting protein

CAP

c-Cbl-associated protein

APMSF

α-amidinophenylmethanesulfonyl fluoride hydrochloride

GST

glutathione S-transferase

SPM

synaptic plasma membrane

DTT

dithiothreitol
- Received June 28, 1999.
- Revision received August 18, 1999.
The American Society for Biochemistry and Molecular Biology, Inc.