title: Sharpin, a novel postsynaptic density protein that directly interacts with the shank family of proteins.
abstract: The Shank family of proteins (also termed CortBP, ProSAP, or Synamon) is highly enriched in the postsynaptic density (PSD) of excitatory synapses in brain. Shank contains multiple domains for protein-protein interactions, including ankyrin repeats, SH3 domain, PDZ domain, SAM domain, and an extensive proline-rich region. We have identified a novel protein, termed Sharpin, that directly interacts with the ankyrin repeats of Shank. Sharpin is enriched in the PSD and forms a complex with Shank in heterologous cells and brain. Immunostaining reveals the presence of Sharpin at excitatory synapses and its colocalization with Shank. While the C-terminal half of Sharpin interacts with Shank, the N-terminal half of Sharpin mediates homomultimerization. Considering the fact that the ankyrin repeats and the SH3 domain of Shank can be truncated by alternative splicing, these results define Sharpin as a novel PSD protein that may regulate the complexity of the Shank-based protein network in an alternative splicing-dependent manner.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Yusong-ku, Daejon, 305-701, Korea.
authors.forename: S
authors.initials: S
authors.lastname: Lim
authors.forename: C
authors.initials: C
authors.lastname: Sala
authors.forename: J
authors.initials: J
authors.lastname: Yoon
authors.forename: S
authors.initials: S
authors.lastname: Park
authors.forename: S
authors.initials: S
authors.lastname: Kuroda
authors.forename: M
authors.initials: M
authors.lastname: Sheng
authors.forename: E
authors.initials: E
authors.lastname: Kim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017487:Ankyrins / Q000378:metabolism; D001923:Brain Chemistry / Q000502:physiology*; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D015870:Gene Expression / Q000502:physiology; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013569:Synapses / Q000737:chemistry / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D017487:Ankyrins; D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C120531:Shank1 protein, rat; C425287:sharpin