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

Rose E. Goodchild, William T. Dauer

Research output: Contribution to journalArticle

158 Scopus citations

Abstract

A glutamic acid deletion (ΔE) 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 ΔE 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.

Original languageEnglish (US)
Pages (from-to)855-862
Number of pages8
JournalJournal of Cell Biology
Volume168
Issue number6
DOIs
StatePublished - Mar 2005

ASJC Scopus subject areas

  • Cell Biology

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