Scribble Scaffolds a Signalosome for Active Forgetting

• Published in: Neuron (Cambridge, Mass.) Mass.), 2016-06, Vol.90 (6), p.1230-1242
• Main Authors: Cervantes-Sandoval, Isaac, Chakraborty, Molee, MacMullen, Courtney, Davis, Ronald L.
• Format: Article
• Language: English
• Subjects: Animals; Cofilin 1 - metabolism; Cytoskeleton; Dopaminergic Neurons - metabolism; Drosophila; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Drosophila Proteins - physiology; Experiments; Gene Knockdown Techniques; Insects; Membrane Proteins - genetics; Membrane Proteins - metabolism; Membrane Proteins - physiology; Memory; Memory - physiology; Memory Disorders - physiopathology; Mushroom Bodies - metabolism; Neurons; Proteins; rac GTP-Binding Proteins - metabolism; Retention; Studies
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2016.05.010

Forgetting, one part of the brain’s memory management system, provides balance to the encoding and consolidation of new information by removing unused or unwanted memories or by suppressing their expression. Recent studies identified the small G protein, Rac1, as a key player in the Drosophila mushroom bodies neurons (MBn) for active forgetting. We subsequently discovered that a few dopaminergic neurons (DAn) that innervate the MBn mediate forgetting. Here we show that Scribble, a scaffolding protein known primarily for its role as a cell polarity determinant, orchestrates the intracellular signaling for normal forgetting. Knocking down scribble expression in either MBn or DAn impairs normal memory loss. Scribble interacts physically and genetically with Rac1, Pak3, and Cofilin within MBn, nucleating a forgetting signalosome that is downstream of dopaminergic inputs that regulate forgetting. These results bind disparate molecular players in active forgetting into a single signaling pathway: Dopamine→ Dopamine Receptor→ Scribble→ Rac→ Cofilin. •Scribble is a Drosophila memory suppressor gene•The gene is expressed and functions in mushroom body and dopaminergic neurons•It is necessary for normal active forgetting•It regulates memory loss by scaffolding a forgetting signalosome Forgetting is a well-regulated function of the brain that allows adaptation to an ever-changing environment. In this study, Cervantes-Sandoval et al. demonstrate that Scribble, identified originally as a cell polarity determinant protein, regulates memory loss by scaffolding a forgetting signalosome.