TY - JOUR
T1 - Mislocalization to the nuclear envelope
T2 - An effect of the dystonia-causing torsinA mutation
AU - Goodchild, Rose E.
AU - Dauer, William T.
PY - 2004/1/20
Y1 - 2004/1/20
N2 - Primary dystonia is a disease characterized by involuntary twisting movements caused by CNS dysfunction without underlying histopathology. DYT1 dystonia is a form of primary dystonia caused by an in-frame GAG deletion (ΔE302/3) in the TOR1A gene that encodes the endoplasmic reticulum luminal protein torsinA. We show that torsinA is also present in the nuclear envelope (NE), where it appears to interact with substrate, and that the ΔE302/3 mutation causes a striking redistribution of torsinA from the endoplasmic reticulum to the NE. In addition, ΔE302/3-torsinA recruits WT torsinA to the NE, potentially providing insight into an understanding of the dominant inheritance of the disease. DYT1 dystonia appears to be a previously uncharacterized NE disease and the first, to our knowledge, to selectively affect CNS function.
AB - Primary dystonia is a disease characterized by involuntary twisting movements caused by CNS dysfunction without underlying histopathology. DYT1 dystonia is a form of primary dystonia caused by an in-frame GAG deletion (ΔE302/3) in the TOR1A gene that encodes the endoplasmic reticulum luminal protein torsinA. We show that torsinA is also present in the nuclear envelope (NE), where it appears to interact with substrate, and that the ΔE302/3 mutation causes a striking redistribution of torsinA from the endoplasmic reticulum to the NE. In addition, ΔE302/3-torsinA recruits WT torsinA to the NE, potentially providing insight into an understanding of the dominant inheritance of the disease. DYT1 dystonia appears to be a previously uncharacterized NE disease and the first, to our knowledge, to selectively affect CNS function.
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U2 - 10.1073/pnas.0304375101
DO - 10.1073/pnas.0304375101
M3 - Article
C2 - 14711988
AN - SCOPUS:1642433201
SN - 0027-8424
VL - 101
SP - 847
EP - 852
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 3
ER -