Ero1-L, an ischemia-inducible gene from rat brain with homology to global ischemia-induced gene 11 (Giig11), is localized to neuronal dendrites by a dispersed identifier (ID) element-dependent mechanism.
Many changes in neuronal gene expression occur in response to ischemia, and these may play a role in determining the fate of ischemic neurons. To identify genes induced in the rat brain following cerebral ischemia, a strategy was used that combines subtractive hybridization and differential screening. Among the genes identified was one referred to as global ischemia-inducible gene 11(Giig11). Sequence analysis indicated that Giig11 exhibited 97% and 91% identity to the known Ero1-L (S. cereviseae ero1-like oxidoreductase) of mouse and human origin, which is involved in oxidative endoplasmic reticulum protein folding. Rat Ero1-L/Giig11 also contains a l07-bp sequence that is nearly identical (> 95%) to the known dispersed repetitive identifier (ID), but which is lacking in mouse and human Ero1-L. Northern blotting showed that expression of the ID element and Ero1-L/Giig11 mRNA increased after global cerebral ischemia. In situ hybridization demonstrated increased expression of Ero1-L/Giig11 in the brain following ischemic injury, with the highest levels in the vulnerable hippocampal CA1 pyramidal neurons. Transfection of cultured primary hippocampal neurons with a plasmid containing green fluorescent protein (gfp) and Ero1-L/Giig11 cDNA (with and without the ID element) produced a gfp-Ero1-L/Giig11 fusion protein, and more fusion protein was localized into dendrites in the presence of the ID element, suggesting that the ID element promotes Ero1-L/Giig11 protein localization to dendrites. Therefore, Ero-1L/Giig11 may have a role in ischemia-induced neuronal repair or survival mechanisms directed at counteracting abnormalities in protein folding, maturation and distribution.
Chen
Dexi
D
R. S. Dow Neurobiology Laboratories, Legacy Research, Portland, Oregon 97232, USA.
Jin
Kunlin
K
Kawaguchi
Kenji
K
Nakayama
Masaki
M
Zhou
Xiaoman
X
Xiong
Zhigang
Z
Zhou
An
A
Mao
Xiao Ou
XO
Greenberg
David A
DA
Graham
Steven H
SH
Simon
Roger P
RP
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism*; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D020071:Interspersed Repetitive Sequences / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017422:Sequence Analysis, DNA; D017385:Sequence Homology
C485766:Ero1a protein, rat; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger