The AAA+ protein torsinA interacts with a conserved domain present in LAP1 and a novel ER protein.
A glutamic acid deletion (DeltaE) in the AAA+ protein torsinA causes DYT1 dystonia. Although the majority of torsinA resides within the endoplasmic reticulum (ER), torsinA binds a substrate in the lumen of the nuclear envelope (NE), and the DeltaE mutation enhances this interaction. Using a novel cell-based screen, we identify ... lamina-associated polypeptide 1 (LAP1) as a torsinA-interacting protein. LAP1 may be a torsinA substrate, as expression of the isolated lumenal domain of LAP1 inhibits the NE localization of "substrate trap" EQ-torsinA and EQ-torsinA coimmunoprecipitates with LAP1 to a greater extent than wild-type torsinA. Furthermore, we identify a novel transmembrane protein, lumenal domain like LAP1 (LULL1), which also appears to interact with torsinA. Interestingly, LULL1 resides in the main ER. Consequently, torsinA interacts directly or indirectly with a novel class of transmembrane proteins that are localized in different subdomains of the ER system, either or both of which may play a role in the pathogenesis of DYT1 dystonia.
Mesh Terms:
Amino Acid Sequence, Animals, Carrier Proteins, Cell Line, Conserved Sequence, Cricetinae, Endoplasmic Reticulum, Fluorescence Recovery After Photobleaching, Green Fluorescent Proteins, HSC70 Heat-Shock Proteins, HSP70 Heat-Shock Proteins, Hela Cells, Humans, Kinetics, Membrane Proteins, Mice, Microscopy, Confocal, Molecular Chaperones, Molecular Sequence Data, Mutation, NIH 3T3 Cells, Nuclear Envelope, Precipitin Tests, Protein Structure, Tertiary, Proteins, Reverse Transcriptase Polymerase Chain Reaction, Sequence Deletion, Sequence Homology, Amino Acid, Transfection
Amino Acid Sequence, Animals, Carrier Proteins, Cell Line, Conserved Sequence, Cricetinae, Endoplasmic Reticulum, Fluorescence Recovery After Photobleaching, Green Fluorescent Proteins, HSC70 Heat-Shock Proteins, HSP70 Heat-Shock Proteins, Hela Cells, Humans, Kinetics, Membrane Proteins, Mice, Microscopy, Confocal, Molecular Chaperones, Molecular Sequence Data, Mutation, NIH 3T3 Cells, Nuclear Envelope, Precipitin Tests, Protein Structure, Tertiary, Proteins, Reverse Transcriptase Polymerase Chain Reaction, Sequence Deletion, Sequence Homology, Amino Acid, Transfection
J. Cell Biol.
Date: Mar. 14, 2005
PubMed ID: 15767459
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