, 2005 and Monyer et al., 1992). By contrast, AMPA receptors are formed by coassembly of the GluA1–GluA4 subunits, each of which can form functional homomeric receptors (Hollmann

et al., 1989 and Keinänen et al., 1990), although in vivo most AMPA receptors contain both the GluA2 subunit and either GluA1, GluA3, or GluA4 (Geiger et al., 1995 and Rossmann et al., 2011). A large number of studies have revealed that control of trafficking plays a key role in regulating iGluR transport to the plasma membrane and synapse (Greger and Esteban, 2007, Mah et al., 2005, Penn et al., 2008, Ren et al., 2003, Shi et al., 2010 and Valluru et al., CDK inhibitor 2005). However, the mechanisms which Protease Inhibitor Library cell line control the assembly of heteromeric glutamate receptors assembled from two or three different gene families are largely unknown but likely to involve multiple stages of regulation before transport comes into play. In particular, dimer assembly by the 380 residue amino terminal domain, which emerges from the ribosome before the ligand binding domain and its associated membrane embedded ion channel segments

plays a key role in determining how subunits coassemble during the early stages of biogenesis. Recent studies on AMPA and NMDA receptors provide compelling evidence for such a role and highlight the complex mechanisms regulating iGluR assembly (Farina et al., 2011, Rossmann et al., 2011 and Shanks

et al., 2010). In this study, we examine the role of the Oxymatrine ATD in assembly of heteromeric kainate receptors assembled from the GluR6 and KA2 subunits, which form the most abundant kainate receptor subtype in the brain (Petralia et al., 1994). We address the issue of whether there exists a unique assembly pattern; define the mechanisms which underlie its formation and which exclude alternative assemblies; and probe the energetics of assembly for heteromeric glutamate receptors. Glutamate receptor ion channels are tetrameric assemblies in which both the ATD and ligand binding domains assemble as a dimer of dimers (Sobolevsky et al., 2009). Because the iGluR ATD dimer of dimers assembly lacks 4-fold rotational symmetry, a receptor generated by coassembly of GluR6 and KA2 subunits could be formed by pairs of homodimers or pairs of heterodimers, and in the latter case, the dimer of dimers interface could be formed by either the GluR6 or KA2 subunits (Figure 1A).