Aggregation Limits Surface Expression of Homomeric GluA3 Receptors

AMPA receptors are glutamate-gated cation channels assembled from GluA1-4 subunits and have properties that are strongly dependent on the subunit composition. The subunits have different propensities to form homomeric or various heteromeric receptors expressed on cell surface, but the underlying mechanisms are still poorly understood. Here, we examined the biochemical basis for the poor ability of GluA3 subunits to form homomeric receptors, linked previously to two amino acid residues, Y454 and R461, in its ligand-binding domain (LBD). Surface expression of GluA3 was improved by co-assembly with GluA2 but not with stargazin, a trafficking chaperone and modulator of AMPA receptors. The secretion efficiency of GluA2 and GluA3 LBDs paralleled the transport difference between the respective full-length receptors and was similarly dependent on Y454/R461, but not on LBD stability. In comparison to GluA2, GluA3 homomeric receptors showed a strong and Y454/R461-dependent tendency to aggregate both in the macroscopic scale measured as lower solubility in nonionic detergent and in the microscopic scale evident as the preponderance of hydrodynamically large structures in density gradient centrifugation and native gel electrophoresis. We conclude that the impaired surface expression of homomeric GluA3 receptors is caused by nonproductive assembly and aggregation to which LBD residues Y454 and R461 strongly contribute. This aggregation inhibits the entry of newly synthesized GluA3 receptors to the secretory pathway.

An accessibility planning tool for network transit oriented development : SNAP

In the academic debate regarding the influences between urban form, built environment and travel patterns, a specific idea that has taken hold is that more compact urban development around railway stations, often referred to as Transit Oriented Development (TOD), contributes to the control of vehicle travel and to more sustainable metropolitan systems. According to this general principle this work proposes a GIS accessibility tool for the design of polycentric transit oriented scenario: SNAP - Station Network Accessibility Planning tool. In the first part the state of the art on Transit Oriented Development policies in Europe is presented with a focus on three study cases. In the second part the SNAP tool is described, with remarks to the approach, the methodology and the used indicators. Furthermore the paper discusses an application to the metropolitan area of Naples.