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The Drosophila radish gene encodes a protein required for anesthesia-resistant memory.

ABSTRACT: Long-term memory in Drosophila is separable into two components: consolidated, anesthesia-resistant memory and long-lasting, protein-synthesis-dependent memory. The Drosophila memory mutant radish is specifically deficient in anesthesia-resistant memory and so represents the only molecular avenue to understanding this memory component. Here, we have identified the radish gene by positional cloning and comparative sequencing, finding a mutant stop codon in gene CG15720 from the Drosophila Genome Project. Induction of a wild-type CG15720 transgene in adult flies acutely rescues the mutant's memory defect. The phospholipase A2 gene, previously identified as radish [Chiang et al. (2004) Curr. Biol. 14:263-272], maps 95 kb outside the behaviorally determined deletion interval and is unlikely to be radish. The Radish protein is highly expressed in the mushroom bodies, centers of olfactory memory. It encodes a protein with 23 predicted cyclic-AMP-dependent protein kinase (PKA) phosphorylation sequences. The Radish protein has recently been reported to bind to Rac1 [Formstecher et al. (2005) Genome Res. 15:376-384], a small GTPase that regulates cytoskeletal rearrangement and influences neuronal and synaptic morphology.

SUBMITTER: Folkers E

PROVIDER: S-EPMC1634833 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Multiple components have been identified that exhibit different stabilities for aversive olfactory memory in Drosophila These components have been defined by behavioral and genetic studies and genes specifically required for a specific component have also been identified. Intermediate-term memory generated after single cycle conditioning is divided into anesthesia-sensitive memory (ASM) and anesthesia-resistant memory (ARM), with the latter being more stable. We determined that the ASM and ARM pathways converged on the Rgk1 small GTPase and that the N-terminal domain-deleted Rgk1 was sufficient for ASM formation, whereas the full-length form was required for ARM formation. Rgk1 is specifically accumulated at the synaptic site of the Kenyon cells (KCs), the intrinsic neurons of the mushroom bodies, which play a pivotal role in olfactory memory formation. A higher than normal Rgk1 level enhanced memory retention, which is consistent with the result that Rgk1 suppressed Rac-dependent memory decay; these findings suggest that rgk1 bolsters ASM via the suppression of forgetting. We propose that Rgk1 plays a pivotal role in the regulation of memory stabilization by serving as a molecular node that resides at KC synapses, where the ASM and ARM pathway may interact.SIGNIFICANCE STATEMENT Memory consists of multiple components. Drosophila olfactory memory serves as a fundamental model with which to investigate the mechanisms that underlie memory formation and has provided genetic and molecular means to identify the components of memory, namely short-term, intermediate-term, and long-term memory, depending on how long the memory lasts. Intermediate memory is further divided into anesthesia-sensitive memory (ASM) and anesthesia-resistant memory (ARM), with the latter being more stable. We have identified a small GTPase in Drosophila, Rgk1, which plays a pivotal role in the regulation of olfactory memory stability. Rgk1 is required for both ASM and ARM. Moreover, N-terminal domain-deleted Rgk1 was sufficient for ASM formation, whereas the full-length form was required for ARM formation.

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The Drosophila radish gene encodes a protein required for anesthesia-resistant memory.

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