CAMP at Perinuclear MAKAPα Signalosomes Is Regulated by Local Ca Signaling in Primary Hippocampal Neurons

Overview

Journal eNeuro

Specialty Neurology

Date 2021 Jan 26

PMID 33495246

Citations 8

Authors

Tomasz Boczek

Qian Yu

Ying Zhu

Kimberly L Dodge-Kafka

Jeffrey L Goldberg

Michael S Kapiloff

Affiliations

Soon will be listed here.

Abstract

The second messenger cyclic adenosine monophosphate (cAMP) is important for the regulation of neuronal structure and function, including neurite extension. A perinuclear cAMP compartment organized by the scaffold protein muscle A-kinase anchoring protein α (mAKAPα/AKAP6α) is sufficient and necessary for axon growth by rat hippocampal neurons Here, we report that cAMP at mAKAPα signalosomes is regulated by local Ca signaling that mediates activity-dependent cAMP elevation within that compartment. Simultaneous Forster resonance energy transfer (FRET) imaging using the protein kinase A (PKA) activity reporter AKAR4 and intensiometric imaging using the RCaMP1h fluorescent Ca sensor revealed that membrane depolarization by KCl selectively induced activation of perinuclear PKA activity. Activity-dependent perinuclear PKA activity was dependent on expression of the mAKAPα scaffold, while both perinuclear Ca elevation and PKA activation were dependent on voltage-dependent L-type Ca channel activity. Importantly, chelation of Ca by a nuclear envelope-localized parvalbumin fusion protein inhibited both activity-induced perinuclear PKA activity and axon elongation. Together, this study provides evidence for a model in which a neuronal perinuclear cAMP compartment is locally regulated by activity-dependent Ca influx, providing local control for the enhancement of neurite extension.

Citing Articles

Perinuclear compartment controls calcineurin/MEF2 signaling for axonal outgrowth of hippocampal neurons.

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