PKA restricts ERK signaling in learning and memory Kenyon cell neurons DOI Creative Commons
James C. Sears, Kendal Broadie

Cellular Signalling, Journal Year: 2025, Volume and Issue: 132, P. 111818 - 111818

Published: April 17, 2025

Protein Kinase A (PKA) and Extracellular Signal-Regulated (ERK) have core roles in learning memory. Here, we investigate kinase-kinase signaling interactions the Drosophila brain Kenyon cell learning/memory circuit using separation of phases-based activity reporter kinase (SPARK) biosensors to image circuit-localized functions vivo. We find that constitutively active Rapidly Accelerated Fibrosarcoma (RAFgof) enhances ERK only domains with low baseline PKA signaling, transgenic inhibition function elevates signaling. Conversely, loss has no impact on whereas RAFgof expands Importantly, together synergistically These findings indicate a negative PKA-ERK pathway interaction within cells. potentiating an exogenous NaChBac ion channel function, uniformly strongly increases Similarly, thermogenetic stimulation temperature-sensitive TRPA1 PKA, (NaChBac) while also inhibiting Likewise, conditional induction (TRPA1) activity-dependent Finally, mechanically-induced seizure model (bang-sensitive sesB mutant) simultaneous this acts increase Taken together, conclude limits cells memory circuit, acting restrict

Language: Английский

Experience-dependent MAPK/ERK signaling in glia regulates critical period remodeling of synaptic glomeruli DOI Creative Commons

Nicholas Baumann,

James C. Sears, Kendal Broadie

et al.

Cellular Signalling, Journal Year: 2024, Volume and Issue: 120, P. 111224 - 111224

Published: May 12, 2024

Early-life critical periods allow initial sensory experience to remodel brain circuitry so that synaptic connectivity can be optimized environmental input. In the Drosophila juvenile brain, olfactory neuron (OSN) glomeruli are pruned by glial phagocytosis in dose-dependent response early odor during a well-defined period. Extracellular signal-regulated kinase (ERK) separation of phases-based activity reporter (SPARK) biosensors reveal experience-dependent signaling glia this Glial ERK-SPARK is depressed removal Draper receptors orchestrating phagocytosis. Cell-targeted genetic knockdown ERK reduces pruning OSN mechanism. Noonan Syndrome caused gain-of-function mutations protein tyrosine phosphatase non-receptor type 11 (PTPN11) inhibiting signaling, and glial-targeted patient-derived mutation increases impairs glomeruli. We conclude period drives required for glomeruli, altered mechanism disease model.

Language: Английский

Citations

7
PKA restricts ERK signaling in learning and memory Kenyon cell neurons DOI Creative Commons
James C. Sears, Kendal Broadie

Cellular Signalling, Journal Year: 2025, Volume and Issue: 132, P. 111818 - 111818

Published: April 17, 2025

Protein Kinase A (PKA) and Extracellular Signal-Regulated (ERK) have core roles in learning memory. Here, we investigate kinase-kinase signaling interactions the Drosophila brain Kenyon cell learning/memory circuit using separation of phases-based activity reporter kinase (SPARK) biosensors to image circuit-localized functions vivo. We find that constitutively active Rapidly Accelerated Fibrosarcoma (RAFgof) enhances ERK only domains with low baseline PKA signaling, transgenic inhibition function elevates signaling. Conversely, loss has no impact on whereas RAFgof expands Importantly, together synergistically These findings indicate a negative PKA-ERK pathway interaction within cells. potentiating an exogenous NaChBac ion channel function, uniformly strongly increases Similarly, thermogenetic stimulation temperature-sensitive TRPA1 PKA, (NaChBac) while also inhibiting Likewise, conditional induction (TRPA1) activity-dependent Finally, mechanically-induced seizure model (bang-sensitive sesB mutant) simultaneous this acts increase Taken together, conclude limits cells memory circuit, acting restrict

Language: Английский

Citations

0