The human GCOM1 complex gene interacts with the NMDA receptor and internexin-alpha

The known functions of the human GCOM1 complex hub gene include transcription elongation and the intercalated disk of cardiac myocytes. However, in all likelihood, the gene's most interesting, and thus far least understood, roles will be found in the central nervous system. To investigate the functions of the GCOM1 gene in the CNS, we have cloned human and rat brain cDNAs encoding novel, 105 kDa GCOM1 combined (Gcom) proteins, designated Gcom15, and identified a new group of GCOM1 interacting genes, termed Gints, from yeast two-hybrid (Y2H) screens. We showed that Gcom15 interacts with the NR1 subunit of the NMDA receptor by co-expression in heterologous cells, in which we observed bi-directional co-immunoprecipitation of human Gcom15 and murine NR1. Our Y2H screens revealed 27 novel GCOM1 interacting genes, many of which are synaptic proteins and/or play roles in neurologic diseases. Finally, we showed, using rat brain protein preparations, that the Gint internexin-alpha (INA), a known interactor of the NMDAR, co-IPs with GCOM1 proteins, suggesting a GCOM1-GRIN1-INA interaction and a novel pathway that may be relevant to neuroprotection

Effect of liraglutide on cardiovascular outcomes in elderly patients: A post hoc analysis of a randomized controlled trial

Background: Comorbidities and complications associ-ated with type 2 diabetes mellitus (T2DM) increase with age, making treatment of elderly persons with this condition chal-lenging. Clinical data on the effect of antihyperglycemic treat-ment on cardiovascular (CV) events in elderly persons are limited (1). The U.S. Food and Drug Administration and Euro-pean Medicines Agency recommend collecting comprehen-sive data on elderly patients with diabetes, particularly those aged 75 years or older, to inform appropriate treatment of this growing populatio

Regulation of the glial glutamate transporter GLT-1 by glutamate and δ-opioid receptor stimulation

AbstractThe excitatory effect of presynaptically released glutamate is tightly regulated and terminated by high affinity sodium-dependent glutamate transporters. The regulation of the glial glutamate transporter GLT-1 is potentially important in synaptic modulation. Using astroglial cultures prepared from the rat cerebral cortex, we found that the δ-opioid receptor agonist [d-pen2,d-pen5]-enkephalin decreases and glutamate increases the expression of the GLT-1 transporter mRNA. Corresponding changes in the uptake kinetics were found after incubation for 48 h with the respective agonists when glial glutamate uptake was measured in primary astroglial cultures. The data suggest that long-term receptor activation induces alterations in glial glutamate uptake properties