Densin-180 Interacts with δ-Catenin/Neural Plakophilin-related Armadillo Repeat Protein at Synapses

• Published in: The Journal of biological chemistry Vol. 277; no. 7; p. 5345
• Main Authors: Ichiro Izawa, Miwako Nishizawa, Kazuhiro Ohtakara, Masaki Inagaki
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 15.02.2002
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M110052200

Densin-180, a protein purified from the postsynaptic density fraction of the rat forebrain, is the founding member of a newly described family of proteins termed the LAP (leucine-rich repeats and PSD-95/Dlg-A/ZO-1 (PDZ) domains) family that plays essential roles in establishment of cell polarity. To identify Densin-180-binding proteins, we screened a yeast two-hybrid library using the carboxyl-terminal fragment of Densin-180 containing PDZ domain as bait, and we isolated δ-catenin/neural plakophilin-related armadillo repeat protein (NPRAP) as a Densin-180-interacting protein. δ-catenin/NPRAP, a member of the armadillo repeat family, is a nervous system-specific adherens junction protein originally discovered as an interactor with presenilin-1, a protein involved in Alzheimer's disease. Densin-180 PDZ domain binds the COOH terminus of δ-catenin/NPRAP containing the PDZ domain-binding sequence. Endogenous Densin-180 was co-immunoprecipitated with δ-catenin/NPRAP and N-cadherin. Although Densin-180 was reported to be a transmembrane protein, Densin-180 was not accessible to surface biotinylation in dissociated hippocampal neurons; hence Densin-180 may be a cytosolic protein. Densin-180 co-localized with δ-catenin/NPRAP at synapses in dissociated hippocampal neurons. We propose that Densin-180 is associated in vivo with δ-catenin/NPRAP and may be involved in organization of the synaptic cell-cell junction through interaction with the δ-catenin/NPRAP-N-cadherin complex.