Rrs1 is involved in endoplasmic reticulum stress response in Huntington disease.
The induction of Rrs1 expression is one of the earliest events detected in a presymptomatic knock-in mouse model of Huntington disease (HD). Rrs1 up-regulation fulfills the HD criteria of dominance, striatal specificity, and polyglutamine dependence. Here we show that mammalian Rrs1 is localized both in the nucleolus as well as in the endoplasmic reticulum (ER) of neurons. This dual localization is shared with its newly identified molecular partner 3D3/lyric. We then show that both genes are induced by ER stress in neurons. Interestingly, we demonstrate that ER stress is an early event in a presymptomatic HD mouse model that persists throughout the life span of the rodent. We further show that ER stress also occurs in postmortem brains of HD patients.
Sector of Neurobiology, International School for Advanced Studies, Via Beirut 2-4, 34151 Trieste, Italy.
Alisia
A
Carnemolla
Elisa
E
Fossale
Elena
E
Agostoni
Silvia
S
Michelazzi
Raffaella
R
Calligaris
Luca
L
De Maso
Giannino
G
Del Sal
Marcy E
ME
MacDonald
Francesca
F
Persichetti
D000818:Animals; D002466:Cell Nucleolus / Q000378:metabolism; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology; D003593:Cytoplasm / Q000378:metabolism; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D055879:Gene Knock-In Techniques; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006816:Huntington Disease / Q000378:metabolism* / Q000473:pathology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins; D013312:Stress, Physiological / Q000502:physiology*; D020798:Two-Hybrid System Techniques
D006360:Heat-Shock Proteins; D008565:Membrane Proteins; C483038:Mtdh protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C544399:RRS1 protein, mouse