The AAA+ protein torsinA interacts with a conserved domain present in LAP1 and a novel ER protein

J Cell Biol. 2005 Mar 14;168(6):855-62. doi: 10.1083/jcb.200411026.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / metabolism
  • Cell Line
  • Conserved Sequence
  • Cricetinae
  • Endoplasmic Reticulum / chemistry
  • Endoplasmic Reticulum / metabolism*
  • Fluorescence Recovery After Photobleaching
  • Green Fluorescent Proteins / metabolism
  • HSC70 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins / chemistry
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism*
  • HeLa Cells
  • Humans
  • Kinetics
  • Membrane Proteins / metabolism
  • Mice
  • Microscopy, Confocal
  • Molecular Chaperones / metabolism*
  • Molecular Sequence Data
  • Mutation
  • NIH 3T3 Cells
  • Nuclear Envelope / metabolism
  • Precipitin Tests
  • Protein Structure, Tertiary
  • Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Deletion
  • Sequence Homology, Amino Acid
  • Transfection

Substances

  • Carrier Proteins
  • HSC70 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • HSPA8 protein, human
  • Hspa8 protein, mouse
  • LAP1 protein, mouse
  • LULL1 protein, mouse
  • Membrane Proteins
  • Molecular Chaperones
  • Proteins
  • TOR1A protein, human
  • TOR1AIP2 protein, human
  • Green Fluorescent Proteins