LY-487379 is a positive allosteric modulator of the metabotropic glutamate receptor mGluR2. EC50 = 1.7 μM. LY-487379 shows no intrinsic agonist or antagonist activity at hmGluR2 and has no activity at human mGluR3. LY-487379 markedly potentiates glutamate-stimulated [35S]GTPγS binding in a concentration-dependent manner at hmGluR2, shifting the glutamate dose-response curve leftward by 3-fold and increasing the maximum levels of [35S]GTPγS stimulation. LY-487379 has anxiolytic effects in fear-potentiated startle. This activity profile is useful in all symptom domains of schizophrenia.
Alternative polyadenylation (APA) produces mRNA isoforms with different 3' UTR lengths. Previous studies indicated that 3' end processing and mRNA export are intertwined in gene regulation. Here, we show that mRNA export factors generally facilitate usage of distal cleavage and
Mitochondria import nearly their entire proteome from the cytoplasm by translocating precursor proteins through the translocase of the outer membrane (TOM) complex. Here, we show dynamic regulation of mitochondrial import by the ubiquitin system. Acute pharmacological inhibition or genetic ablation
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