Ras-association domain of sorting nexin 27 is critical for regulating expression of GIRK potassium channels

G protein-gated inwardly rectifying potassium (GIRK) channels play an important role in regulating neuronal excitability. Sorting nexin 27b (SNX27b), which reduces surface expression of GIRK channels through a PDZ domain interaction, contains a putative Ras-association (RA) domain with unknown function. Deleting the RA domain in SNX27b (SNX27b-DRA) prevents the down-regulation of GIRK2c/GIRK3 channels. Similarly, a point mutation (K305A) in the RA domain disrupts regulation of GIRK2c/GIRK3 channels and reduces H-Ras binding in vitro. Finally, the dominant-negative H-Ras (S17N) occludes the SNX27b-dependent decrease in surface expression of GIRK2c/GIRK3 channels. Thus, the presence of a functional RA domain and the interaction with Ras-like G proteins comprise a novel mechanism for modulating SNX27b control of GIRK channel surface expression and cellular excitability

Young children’s imagination in science education and education for sustainability

This research is concerned with how children's processes of imagination, situated in cultural and social practices, come into play when they invent, anticipate, and explore a problem that is important to them. To enhance our understanding of young children's learning and meaning-making related to science and sustainability, research that investigates children's use of imagination is valuable. The specific aim of this paper is to empirically scrutinize how children's imaginations emerge, develop, and impact their experiences in science. We approach imagination as a situated, open, and unscripted act that emerges within transactions. This empirical study was conducted in a Swedish pre-school, and the data was collected in between' a science inquiry activity and lunchtime. We gathered specific video-sequences wherein the children, lived through the process of imagination, invented a problem together and produced something new. Our analysis showed that imagination has a great significance when children provide different solutions which may be useful in the future to sustainability-related problems. If the purpose of an educational experience in some way supports children's imaginative flow, then practicing an open, listening approach becomes vital. Thus, by encouraging children to explore their concerns and questions related to sustainability issues more thoroughly without incautious recommendations or suggestions from adults, the process of imagination might flourish.</p

Crystal structure of a Kir3.1-prokaryotic Kir channel chimera

The Kir3.1 K+ channel participates in heart rate control and neuronal excitability through G-protein and lipid signaling pathways. Expression in Escherichia coli has been achieved by replacing three fourths of the transmembrane pore with the pore of a prokaryotic Kir channel, leaving the cytoplasmic pore and membrane interfacial regions of Kir3.1 origin. Two structures were determined at 2.2 Å. The selectivity filter is identical to the Streptomyces lividans K+ channel within error of measurement (r.m.s.d.<0.2 Å), suggesting that K+ selectivity requires extreme conservation of three-dimensional structure. Multiple K+ ions reside within the pore and help to explain voltage-dependent Mg2+ and polyamine blockade and strong rectification. Two constrictions, at the inner helix bundle and at the apex of the cytoplasmic pore, may function as gates: in one structure the apex is open and in the other, it is closed. Gating of the apex is mediated by rigid-body movements of the cytoplasmic pore subunits. Phosphatidylinositol 4,5-biphosphate-interacting residues suggest a possible mechanism by which the signaling lipid regulates the cytoplasmic pore

The role of G proteins in assembly and function of Kir3 inwardly rectifying potassium channels

Kir3 channels (also known as GIRK channels) are important regulators of electrical excitability in both cardiomyocytes and neurons. Much is known regarding the assembly and function of these channels and the roles that their interacting proteins play in controlling these events. Further, they are one of the best-studied effectors of heterotrimeric G proteins in general and Gβγ subunits in particular. However, our understanding of the roles of multiple Gβγ binding sites on Kir3 channels is still rudimentary. We discuss potential roles for Gβγ in channel assembly and trafficking in addition to their known role in cellular signaling