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¹ Department of Neurology, Columbia University, New York, NY 10032
² Department of Pharmacology, Columbia University, New York, NY 10032

Correspondence to William Dauer: wtd3{at}columbia.edu

Abstract
A glutamic acid deletion (E) 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 E 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.

Abbreviations used in this paper: LAP1, lamina-associated polypeptide 1; LULL1, lumenal domain like LAP1; NE, nuclear envelope; PDI, protein disulphide isomerase; ROI, region of interest; WCL, whole cell lysate; WT, wild-type.

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