Scribble Scaffolds a Signalosome for Active Forgetting.
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.
Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458, USA. Electronic address: isandova@scripps.edu.
Isaac
I
Cervantes-Sandoval
Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458, USA.
Molee
M
Chakraborty
Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458, USA.
Courtney
C
MacMullen
Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458, USA. Electronic address: rdavis@scripps.edu.
Ronald L
RL
Davis
D000818:Animals; D051338:Cofilin 1 / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000503:physiopathology*; D024521:Mushroom Bodies / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism
D051338:Cofilin 1; D029721:Drosophila Proteins; D008565:Membrane Proteins; C090146:Rac1 protein, Drosophila; C404683:Scrib protein, Drosophila; D020744:rac GTP-Binding Proteins