A novel ubiquitin‐specific protease, synUSP, is localized at the post‐synaptic density and post‐synaptic lipid raft

• Published in: Journal of neurochemistry 2003-11, Vol.87 (3), p.665-675
• Main Authors: Tian, Qing Bao, Okano, Akira, Nakayama, Kohzo, Miyazawa, Shoko, Endo, Shogo, Suzuki, Tatsuo
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Biochemistry and metabolism; Biological and medical sciences; Brain Chemistry; Cells, Cultured; Central nervous system; Cloning, Molecular; Dendrites - metabolism; de‐ubiquitination; Endopeptidases - genetics; Endopeptidases - metabolism; Fundamental and applied biological sciences. Psychology; lipid raft; Membrane Microdomains - metabolism; Molecular Sequence Data; Mutagenesis, Site-Directed; Neurons - cytology; Neurons - metabolism; post‐synaptic density; Rats; Rats, Wistar; RNA, Messenger - metabolism; Sequence Homology, Amino Acid; Subcellular Fractions - chemistry; Subcellular Fractions - metabolism; synapse; Synapses - metabolism; ubiquitin; Ubiquitin-Specific Proteases; ubiquitin‐specific protease; Vertebrates: nervous system and sense organs
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2003.02024.x

Recent reports suggest an important role for protein ubiquitination in synaptic plasticity. We cloned, from the rat brain, a novel gene that encoded an ubiquitin‐specific protease (USP), and termed this protein synaptic ubiquitin‐specific protease (synUSP, GenBankTM Accession no. AB073880). The homologous human gene was mapped to a locus on chromosome 1p36.12. The deduced synUSP protein consisted of 1036 amino acids, and possessed an ubiquitin‐like domain at the C‐terminus, Cys‐ and His‐boxes, leucine zipper motifs, and six amino acid‐repeats of L/ILCPHG. The protein possessed de‐ubiquitinating activity toward a model substrate, as expected from its sequence. The protein of 125 kDa was present in the rat brain; in particular, it was enriched in the post‐synaptic density and the dendritic lipid raft fractions. The immunostaining of cortical neurons confirmed the post‐synaptic localization. The mRNA for synUSP was localized to dendrites, as well as somas, of neuronal cells. Thus, both the mRNA and the protein were localized in the post‐synaptic compartments. These results suggest a regulatory mechanism for the ubiquitin‐related system at the post‐synaptic sites.