Washington University in St. Louis

New Publication by the Hanson Lab

Congratulations to Phyllis and her team on their new publication in the Journal of Cell Science!


Goodchild, RE, Buchwalter, AL, Naismith, TV, Halbrook, K, Billion, K, Dauer, WT, Liang, CC, Dear, ML, and Hanson, PI.  (2015)  Access of torsinA to the inner nuclear membrane is activity dependent and regulated in the endoplasmic reticulum.  Journal of Cell Science  [E-published June 19]

Abstract:  TorsinA is a membrane-embedded AAA+ ATPase important in the nuclear envelope (NE) lumen. However, most torsinA is localized in the peripheral endoplasmic reticulum (ER) lumen with slow mobility incompatible with free equilibration between ER subdomains. We now find that NE-localized torsinA is on the inner nuclear membrane (INM) and ask how torsinA reaches this subdomain. The ER system contains two transmembrane proteins, LAP1 and LULL1, that reversibly co-assemble with and activate torsinA. Whereas LAP1 localizes on the INM, we show that LULL1 is in the peripheral ER and does not enter the INM. Paradoxically, interaction between torsinA and LULL1 in the ER targets torsinA to the INM. Native gel electrophoresis reveals torsinA oligomeric complexes that are decreased by LULL1. Mutations in torsinA or LULL1 that inhibit ATPase activity reduce torsinA access to the INM. Furthermore, although LULL1 binds torsinA in the ER lumen, its effect on torsinA localization requires cytosolic domain mediated oligomerization. These data suggest that LULL1 oligomerizes to engage and transiently disassemble torsinA oligomers, and is thereby positioned to transduce cytoplasmic signals to the INM via torsinA.

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