Scribble scaffolds a signalosome for active forgetting

By Isaac Cervantes-Sandoval, M. Chakraborty, Courtney Macmullen, Ronald L. Davis. 2016

96 citations recorded by the source corpus.

SUMMARY 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.

Subfields: Cellular and Molecular Neuroscience, Materials Chemistry, Plant Science

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. Yi Zhong
2. Qian Li
3. Liyuan Wang
4. Xuchen Zhang
5. Jun Zhu
6. Bohan Zhao
7. Hang Su
8. Xingxing Zhang

In Materials Chemistry

1. Yi Zhong
2. Jun Zhu
3. Hang Su

In Plant Science

1. Yi Zhong
2. Ronald L. Davis

Citations in the corpus

• Incorporating neuro-inspired adaptability for continual learning in artificial intelligence (2023, positive): “Besides, old memories can be actively forgotten for better adapting to a new memory 19,25,28,32 .”
• Genetic dissection of mutual interference between two consecutive learning tasks in Drosophila (2022, background): “Of these molecules, Scribble and SLC22A, have also been reported to regulate Pro-I (Cervantes-Sandoval et al., 2016; Gai et al., 2016).”
• Genetic dissection of active forgetting in labile and consolidated memories in Drosophila (2019, background): “Rac1-mediated forgetting is partially explained by activating cofilin, an actin depolymerization factor, through a PAK/LIMK signaling cascade (3, 17).”
• The Biology of Forgetting – A Perspective (2017, background): “Rac1-dependent forgetting of anesthesia-sensitive memory has also been mapped to the a/b and g MB neurons (Shuai et al., 2010; Berry et al., 2012; Cervantes-Sandoval et al., 2016).”
• Active Protection: Learning-Activated Raf/MAPK Activity Protects Labile Memory from Rac1-Independent Forgetting. (2018, unknown): “Associative experiences such as interference and reversal learning act through active forgetting to accelerate memory decay (Cervantes-Sandoval et al., 2016; Liu et al., 2016b; Shuai et al., 2010; Zhang et al., 2016).”
• The Persistence and Transience of Memory. (2017, background): “…work has provided evidence that this pathway is modulated by dopamine (via dopamine receptor activation and the scaffolding protein Scribble), and thus provides a link between different behavioral states (e.g., sleep) and transience (Berry et al., 2012, 2015; Cervantes-Sandoval et al., 2016).”
• Neuronal mechanisms underlying innate and learned olfactory processing in Drosophila. (2019, background): “305 In forgetting, another receptor, Dop1R2 (aka damb), activates Rac1 and Scribbled via a 306 different G protein, Gq [98-100].”