The serotonergic system plays a key role in regulating basic behaviors. Deficits in serotonergic neurotransmission have been implicated in psychiatric disorders, such as schizophrenia and depression. Here we have optimized a behavioral screen and performed a small scale genetic screen to identify genes involved in serotonin responsiveness in the mouse.… (More)
The diaphanous gene is the founding member of a family of Diaphanous-related formin proteins (DRFs). We identified diaphanous in a screen for genes that are necessary for the normal growth and stabilization of the Drosophila neuromuscular junction (NMJ). Here, we demonstrate that diaphanous mutations perturb synaptic growth at the NMJ. Diaphanous protein is… (More)
Adrenergic stimulation of the heart engages cAMP and phosphoinositide second messenger signaling cascades. Cardiac phosphoinositide 3-kinase p110γ participates in these processes by sustaining β-adrenergic receptor internalization through its catalytic function and by controlling phosphodiesterase 3B (PDE3B) activity via an unknown kinase-independent… (More)
PKA is retained within distinct subcellular environments by the association of its regulatory type II (RII) subunits with A-kinase anchoring proteins (AKAPs). Conventional reagents that universally disrupt PKA anchoring are patterned after a conserved AKAP motif. We introduce a phage selection procedure that exploits high-resolution structural information… (More)
A cell's response to its environment is often determined by signaling through the actions of enzyme cascades. The ability to organize these enzymes into multiprotein complexes allows for a high degree of fidelity, efficiency and spatial precision in signaling responses.
Background: Protein Kinase A (PKA) is confined to subcellular compartments by A-Kinase Anchoring Proteins (AKAPs) Results: A structure-based phage directed evolution strategy has yielded modified type II PKA regulatory subunits with AKAP-selective binding properties Conclusion: Engineered R Select proteins preferentially target particular AKAP-PKA… (More)
Background: PKA is confined to subcellular compartments by A-kinase anchoring proteins (AKAPs). Results: A structure-based phage-directed evolution strategy has yielded modified PKA regulatory type II subunits with AKAP-selective binding properties. Conclusion: Engineered R Select proteins preferentially target particular AKAP-PKA interfaces Significance: R… (More)