Protei
n SUMOylatio
n has bee
n implicated i
n the pathoge
nesis of ischemic stro
ke. However, the u
nderlyi
ng mecha
nisms remai
n u
nclear. Here, we fou
nd that global brai
n ischemia evo
kes a sustai
ned elevatio
n of GluK2 SUMOylatio
n i
n the rat hippocampal CA1 regio
n. Over-expressio
n of wild-type GluK2, but
not SUMOylatio
n-deficie
nt muta
nt, sig
nifica
ntly i
ncreased the activity of MLK3 a
nd JNK3 after
kai
nate stimulatio
n. SUMOylatio
n deficie
ncy atte
nuated the
kai
nate-stimulated i
nteractio
n betwee
n MLK3 a
nd GluK2. I
n additio
n, i
nhibitio
n of
kai
nate-evo
ked GluK2 e
ndocytosis decreased the activatio
n of MLK3-JNK3 sig
nali
ng a
nd the bi
ndi
ng of MLK3-GluK2 i
n cultured cortical
neuro
ns. These results suggest that the i
nter
nalizatio
n of GluK2 followi
ng SUMO modificatio
n promotes its bi
ndi
ng with MLK3, thereby activati
ng the MLK3-JNK3 pathway, which may be respo
nsible for ischemic
neuro
nal cell death.
Structured summary of protein interactions
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