A reelin–integrin receptor interaction regulates Arc mRNA translation in synaptoneurosomes
AUTOR(ES)
Dong, Erbo
FONTE
The National Academy of Sciences
RESUMO
Reelin is synthesized and secreted into extracellular matrix by cortical γ-aminobutyric acid (GABA)ergic interneurons and binds with high affinity to the extracellular domain of integrin receptors expressed in dendritic shaft and spine postsynaptic densities (DSPSD) of pyramidal neurons. In heterozygous reeler mice, reelin bound to DSPSD, and the expression of Arc (activity-regulated cytoskeletal protein) is lower than in wild-type mice. We studied the effect of reelin on Arc and total protein synthesis in synaptoneurosomes (SNSs) prepared from mouse neocortex. Recombinant full-length mouse reelin displaces the high affinity (KD = 60 fM) binding of [125I]echistatin (a competitive integrin receptor antagonist) to integrin receptors with a Ki of 22 pM and with a Hill slope close to 1. Echistatin (50–100 nM) competitively antagonizes and abates reelin binding. The addition of reelin (2–40 pM) to SNSs enhances the incorporation of [35S]methionine into Arc and other rapidly translated proteins in a concentration-dependent manner. This incorporation is virtually abolished by 50–100 nM echistatin or by 5–10 nM rapamycin, a blocker of the mammalian target of rapamycin kinase. We conclude that reelin binds with high affinity to integrin receptors expressed in SNSs and thereby activates Arc protein synthesis.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=154370Documentos Relacionados
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