A reelin-integrin receptor interaction regulates Arc mRNA translation in synaptoneurosomes.
Reelin is synthesized and secreted into extracellular matrix by cortical gamma-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 (K(D) = 60 fM) binding of [(125)I]echistatin (a competitive integrin receptor antagonist) to integrin receptors with a K(i) 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 [(35)S]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.
Dong
Erbo
E
Psychiatric Institute, Department of Psychiatry, University of Illinois, College of Medicine, Chicago, IL 60612, USA.
Caruncho
Hector
H
Liu
Wen Sheng
WS
Smalheiser
Neil R
NR
Grayson
Dennis R
DR
Costa
Erminio
E
Guidotti
Alessandro
A
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002460:Cell Line; D017931:DNA Primers; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D008715:Methionine / Q000378:metabolism; D051379:Mice; D008854:Microscopy, Electron; D009124:Muscle Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins; D010455:Peptides / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases; D013574:Synaptosomes / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D015816:Cell Adhesion Molecules, Neuronal; D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D016023:Integrins; D036341:Intercellular Signaling Peptides and Proteins; D009124:Muscle Proteins; C112246:NOL3 protein, human; D009419:Nerve Tissue Proteins; C491787:Nol3 protein, mouse; D010455:Peptides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D000091042:Reelin Protein; C057986:echistatin; D008715:Methionine; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases