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5'-Adenosine monophosphate-activated protein kinase (AMPK) is a master metabolic regulator that has been shown to inhibit the establishment of neuronal polarity/axogenesis under energy stress conditions, whereas brain-specific kinase (BRSK) promotes the establishment of axon-dendrite polarity and synaptic development. However, little information exists regarding the localized activity and regulation of these kinases in developing neurons. In this study, using a fluorescence resonance energy transfer (FRET)-based activity reporter that responds to both AMPK and BRSK, we found that BRSK activity is elevated in the distal region of axons in polarized hippocampal neurons before any stimulation and does not respond to either Ca(2+) or 2-deoxyglucose (2-DG) stimulation. In contrast, AMPK activity is stimulated by either Ca(2+) or 2-DG in the soma, dendrites, and axons of hippocampal neurons, with maximal stimulated activity observed in the distal region of the axon. Our study shows that the activities of both AMPK and BRSK are polarized in developing hippocampal neurons, with high levels in the distal region of extended axons.

Polarized activities of AMPK and BRSK in primary hippocampal neurons