Group I metabotropic glutamate (mGlu) receptors (mGlu1/5 subtypes) are G protein-coupled receptors and are broadly expressed in the mammalian brain. These receptors play key roles in the modulation of normal glutamatergic transmission and synaptic plasticity, and abnormal mGlu1/5 signaling is linked to the pathogenesis and symptomatology of various mental and neurological disorders. Group I mGlu receptors are noticeably regulated via a mechanism involving dynamic protein–protein interactions. Several synaptic protein kinases were recently found to directly bind to the intracellular domains of mGlu1/5 receptors and phosphorylate the receptors at distinct amino acid residues. A variety of scaffolding and adaptor proteins also interact with mGlu1/5. Constitutive or activity-dependent interactions between mGlu1/5 and their interacting partners modulate trafficking, anchoring, and expression of the receptors. The mGlu1/5-associated proteins also finetune the efficacy of mGlu1/5 postreceptor signaling and mGlu1/5-mediated synaptic plasticity. This review analyzes the data from recent studies and provides an update on the biochemical and physiological properties of a set of proteins or molecules that interact with and thus regulate mGlu1/5 receptors.

Major depressive disorder is a chronic psychiatric disease with a high prevalence. Brain mechanisms for depression at cellular and molecular levels are far from clear. Increasing evidence from clinical and preclinical studies reveals critical roles of the non-receptor tyrosine kinase (nRTK) superfamily in the pathophysiology, symptomatology, and therapy of depression. To date, several nRTK members from three nRTK subfamilies, i.e., the Src family kinase (SFK), the Janus tyrosine kinase (JAK) and the focal adhesion kinase (FAK) subfamilies, may connect to the intracellular, intranuclear, and synaptic signaling network linking chronic stress to depression-and anxiety-like behavior. These SFK/JAK/FAK nRTKs are abundantly expressed in the prefrontal cortex and hippocampus, two core limbic regions implicated in depression, and are enriched at synaptic sites. In various acute or chronic animal models of depression, the nRTKs were significantly altered (up-or downregulated) in their phosphorylation, expression, subcellular/subsynaptic distribution, and/or function. Stress that precipitates depressive behavior also in luenced the interaction of nRTKs with other signaling molecules and downstream substrates, including ionotropic and metabotropic glutamate receptors. The commonly-used antidepressants showed the ability to alter nRTK activity. In sum, the limbic SFK/JAK/FAK nRTKs are sensitive to stress and undergo drastic adaptations in response to chronic depression. These long-lasting adaptations contribute to the remodeling of signaling network or synaptic plasticity critical for the vulnerability to depression and the therapeutic e ficacy of antidepressants.

Background: The hemoglobin A1c is critical for monitoring and managing type II diabetes and providing clinicians with a framework for a treatment plan. Our study analyzes compliance to the American Diabetes Association (ADA) standards of appropriate A1c monitoring and encourages other clinics to monitor the same information within their own clinics. Methods: A retrospective chart review was conducted on all patients who visited the Sojourner Health Clinic between January 2017 and November 2019. All patients who had met the criteria for A1c screening based on recommendations from the ADA were included in the study, as well as patients who were charted as diabetic or pre-diabetic. A total of 88 patients met the criteria for this study. Data collected included patient documentation as diabetic or pre-diabetic and patients’ three most recent A1c values with corresponding dates. Based on this data, these patients were categorized as diabetic, pre-diabetic, or non-diabetic, and were evaluated on whether their A1c was monitored at appropriate intervals. Results: A total of 21.6% of patients were monitored appropriately for their diabetic status determined by their A1c values. Only 18.2% of diabetic patients were accurately monitored. Patients with an unknown diabetic status had the lowest rate of appropriate monitoring. Conclusions: Most patients at the Sojourner Health Clinic are not properly monitored for diabetes using the clinic's modified A1c monitoring guidelines. The clinic can make several improvements to strengthen adherence to these guidelines with the implementation of new protocols for better A1c monitoring. Further studies should be made to assess the efficacy of these changes.