Post-transcriptional regulation and subcellular localization of G-protein γ7 subunit: implications for striatal function and behavioral responses to cocaine.

The striatal D dopamine receptor (DR) and A adenosine receptor (AR) signaling pathways play important roles in drug-related behaviors. These receptors activate the G protein comprised of a specific combination of αβγ subunits. During assembly, the γ subunit sets the cellular level of the G protein.

Selective Manipulation of G-Protein γ Subunit in Mice Provides New Insights into Striatal Control of Motor Behavior.

Stimulatory coupling of dopamine D (DR) and adenosine A receptors (AR) to adenylyl cyclase within the striatum is mediated through a specific Gαβγ heterotrimer to ultimately modulate motor behaviors. To dissect the individual roles of the Gαβγ heterotrimer in different populations of medium spiny neurons (MSNs), we produced and characterized conditional mouse models, in which the gene was deleted in either the DR- or AR/DR-expressing MSNs. We show that conditional loss of γ disrupts the cell type-specific assembly of the Gαβγ heterotrimer, thereby identifying its circumscribed roles acting downstream of either the DRs or ARs in coordinating motor behaviors, including responses to psychostimulants.

Measuring Membrane Lipid Turnover with the pH-sensitive Fluorescent Lipid Analog ND6.

Exo-/endocytosis is a common process mediating the exchange of biomolecules between cells and their environment and among different cells. Specialized cells use this process to execute vital body functions such as insulin secretion from β cells and neurotransmitter release from chemical synapses. Owing to its physiological significance, exo-/endocytosis has been one of the most studied topics in cell biology.

Solvatochromic and pH-Sensitive Fluorescent Membrane Probes for Imaging of Live Cells.

Membrane trafficking is essential for all cells, and visualizing it is particularly useful for studying neuronal functions. Here we report the synthesis, characterization, and application of several membrane- and pH-sensitive probes suitable for live-cell fluorescence imaging. These probes are based on a 1,8-naphthalimide fluorophore scaffold.

REV-ERBα Regulates T17 Cell Development and Autoimmunity.

RORγt is well recognized as the lineage-defining transcription factor for T helper 17 (T17) cell development. However, the cell-intrinsic mechanisms that negatively regulate T17 cell development and autoimmunity remain poorly understood. Here, we demonstrate that the transcriptional repressor REV-ERBα is exclusively expressed in T17 cells, competes with RORγt for their shared DNA consensus sequence, and negatively regulates T17 cell development via repression of genes traditionally characterized as RORγt dependent, including Il17a.