1.γ-aminobutyric acid type A (GABAA) receptor subunits play a direct structural role in synaptic contact formation via their N-terminal extracellular domains.
Brown LE1, Nicholson MW2, Arama JE1, Mercer A1, Thomson AM1, Jovanovic JN3. J Biol Chem. 2016 Apr 20. pii: jbc.M116.714790. [Epub ahead of print]
The establishment of cell-cell contacts between presynaptic GABAergic neurons and their postsynaptic targets initiates the process of GABAergic synapse formation. GABAA receptors (GABAARs), the main postsynaptic receptors for GABA, have been recently demonstrated to act as synaptogenic proteins that can single-handedly induce the formation and functional maturation of inhibitory synapses. To establish how the subunit composition of GABAARs influences their ability to induce synaptogenesis, a co-culture model system incorporating GABAergic medium spiny neurons (MSNs) and the HEK293 cells, stably expressing different combinations of receptor subunits, was developed. Analyses of HEK293 cells innervation by MSN axons using immunocytochemistry, activity-dependent labeling and electrophysiology have indicated that γ2 subunit is required for the formation of active synapses and that its effects are influenced by the type of α/β subunits incorporated into the functional receptor.
2.RhoC is a Potent Regulator of Glutamine Metabolism and N-acetylaspartate Production in Inflammatory Breast Cancer Cells.
Wynn ML1, Yates JA1, Evans CR1, Van Wassenhove L2, Wu ZF1, Bridges S1, Bao L1, Fournier C1, Ashrafzadeh S1, Merrins MJ3, Satin LS1, Schnell S1, Burant CF1, Merajver SD4. J Biol Chem. 2016 Apr 25. pii: jbc.M115.703959. [Epub ahead of print]
Inflammatory breast cancer (IBC) is an extremely lethal cancer that rapidly metastasizes. While the molecular attributes of IBC have been described, little is known about the underlying metabolic features of the disease. Using a variety of metabolic assays including 13C tracer experiments, we found that SUM149 cells, the primary in vitro model of IBC, exhibit metabolic abnormalities that distinguish them from other breast cancer cells, including elevated levels of N-acetylaspartate (NAA), a metabolite primarily associated with neuronal disorders and gliomas. Here we provide the first evidence of NAA in breast cancer. We also report that the oncogene RhoC, a driver of metastatic potential, modulates glutamine and N-acetylaspartate metabolism in IBC cells in vitro, revealing a novel role for RhoC as a regulator of tumor cell metabolism that extends beyond its well-known role in cytoskeletal rearrangement.