AMPK activation regulates neuronal structure in developing hippocampal neurons

S. Ramamurthy, E. Chang, Y. Cao, J. Zhu, G. V. Ronnett

Research output: Contribution to journalArticle

Abstract

AMP-activated protein kinase (AMPK) is a serine/threonine kinase that functions as a cellular and whole organism energy sensor to regulate ATP-consuming (anabolic) and ATP-generating (catabolic) pathways. The heterotrimeric AMPK complex consists of a catalytic α-subunit, regulatory β-subunit, and an AMP/ATP-binding γ-subunit. Several alternate isoforms exist for each subunit (α1, α2, β1, β2, γ1, γ2 and γ3). However, little is known of the expression pattern or function of the individual catalytic complexes in regulating neuronal structure. In this study, we examined the role of AMPK subunits in differentiating hippocampal neurons. We found that during development, the expression of AMPK subunits increase and that activation of AMPK by energetic stress inhibits neuronal development at multiple stages, not only during axon outgrowth, but also during dendrite growth and arborization. The presence of a single functional AMPK catalytic complex was sufficient to mediate these inhibitory effects of energetic stress. Activation of AMPK mediates these effects by suppressing both the mTOR and Akt signaling pathways. These findings demonstrate that the energy-sensing AMPK pathway regulates neuronal structure in distinct regions of developing neurons at multiple stages of development.

Original languageEnglish (US)
Pages (from-to)13-24
Number of pages12
JournalNeuroscience
Volume259
DOIs
StatePublished - Feb 4 2014
Externally publishedYes

Fingerprint

AMP-Activated Protein Kinases
Neurons
Adenosine Triphosphate
Protein Subunits
Neuronal Plasticity
Protein-Serine-Threonine Kinases
Adenosine Monophosphate
Catalytic Domain
Protein Isoforms
Growth

Keywords

  • AMPK
  • Axon
  • Dendrite
  • Development
  • Metabolism
  • Neuron

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

AMPK activation regulates neuronal structure in developing hippocampal neurons. / Ramamurthy, S.; Chang, E.; Cao, Y.; Zhu, J.; Ronnett, G. V.

In: Neuroscience, Vol. 259, 04.02.2014, p. 13-24.

Research output: Contribution to journalArticle

Ramamurthy, S. ; Chang, E. ; Cao, Y. ; Zhu, J. ; Ronnett, G. V. / AMPK activation regulates neuronal structure in developing hippocampal neurons. In: Neuroscience. 2014 ; Vol. 259. pp. 13-24.
@article{647dbb9f2cf84fc6bee1a4c9264e5163,
title = "AMPK activation regulates neuronal structure in developing hippocampal neurons",
abstract = "AMP-activated protein kinase (AMPK) is a serine/threonine kinase that functions as a cellular and whole organism energy sensor to regulate ATP-consuming (anabolic) and ATP-generating (catabolic) pathways. The heterotrimeric AMPK complex consists of a catalytic α-subunit, regulatory β-subunit, and an AMP/ATP-binding γ-subunit. Several alternate isoforms exist for each subunit (α1, α2, β1, β2, γ1, γ2 and γ3). However, little is known of the expression pattern or function of the individual catalytic complexes in regulating neuronal structure. In this study, we examined the role of AMPK subunits in differentiating hippocampal neurons. We found that during development, the expression of AMPK subunits increase and that activation of AMPK by energetic stress inhibits neuronal development at multiple stages, not only during axon outgrowth, but also during dendrite growth and arborization. The presence of a single functional AMPK catalytic complex was sufficient to mediate these inhibitory effects of energetic stress. Activation of AMPK mediates these effects by suppressing both the mTOR and Akt signaling pathways. These findings demonstrate that the energy-sensing AMPK pathway regulates neuronal structure in distinct regions of developing neurons at multiple stages of development.",
keywords = "AMPK, Axon, Dendrite, Development, Metabolism, Neuron",
author = "S. Ramamurthy and E. Chang and Y. Cao and J. Zhu and Ronnett, {G. V.}",
year = "2014",
month = "2",
day = "4",
doi = "10.1016/j.neuroscience.2013.11.048",
language = "English (US)",
volume = "259",
pages = "13--24",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - AMPK activation regulates neuronal structure in developing hippocampal neurons

AU - Ramamurthy, S.

AU - Chang, E.

AU - Cao, Y.

AU - Zhu, J.

AU - Ronnett, G. V.

PY - 2014/2/4

Y1 - 2014/2/4

N2 - AMP-activated protein kinase (AMPK) is a serine/threonine kinase that functions as a cellular and whole organism energy sensor to regulate ATP-consuming (anabolic) and ATP-generating (catabolic) pathways. The heterotrimeric AMPK complex consists of a catalytic α-subunit, regulatory β-subunit, and an AMP/ATP-binding γ-subunit. Several alternate isoforms exist for each subunit (α1, α2, β1, β2, γ1, γ2 and γ3). However, little is known of the expression pattern or function of the individual catalytic complexes in regulating neuronal structure. In this study, we examined the role of AMPK subunits in differentiating hippocampal neurons. We found that during development, the expression of AMPK subunits increase and that activation of AMPK by energetic stress inhibits neuronal development at multiple stages, not only during axon outgrowth, but also during dendrite growth and arborization. The presence of a single functional AMPK catalytic complex was sufficient to mediate these inhibitory effects of energetic stress. Activation of AMPK mediates these effects by suppressing both the mTOR and Akt signaling pathways. These findings demonstrate that the energy-sensing AMPK pathway regulates neuronal structure in distinct regions of developing neurons at multiple stages of development.

AB - AMP-activated protein kinase (AMPK) is a serine/threonine kinase that functions as a cellular and whole organism energy sensor to regulate ATP-consuming (anabolic) and ATP-generating (catabolic) pathways. The heterotrimeric AMPK complex consists of a catalytic α-subunit, regulatory β-subunit, and an AMP/ATP-binding γ-subunit. Several alternate isoforms exist for each subunit (α1, α2, β1, β2, γ1, γ2 and γ3). However, little is known of the expression pattern or function of the individual catalytic complexes in regulating neuronal structure. In this study, we examined the role of AMPK subunits in differentiating hippocampal neurons. We found that during development, the expression of AMPK subunits increase and that activation of AMPK by energetic stress inhibits neuronal development at multiple stages, not only during axon outgrowth, but also during dendrite growth and arborization. The presence of a single functional AMPK catalytic complex was sufficient to mediate these inhibitory effects of energetic stress. Activation of AMPK mediates these effects by suppressing both the mTOR and Akt signaling pathways. These findings demonstrate that the energy-sensing AMPK pathway regulates neuronal structure in distinct regions of developing neurons at multiple stages of development.

KW - AMPK

KW - Axon

KW - Dendrite

KW - Development

KW - Metabolism

KW - Neuron

UR - http://www.scopus.com/inward/record.url?scp=84891066832&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84891066832&partnerID=8YFLogxK

U2 - 10.1016/j.neuroscience.2013.11.048

DO - 10.1016/j.neuroscience.2013.11.048

M3 - Article

C2 - 24295634

AN - SCOPUS:84891066832

VL - 259

SP - 13

EP - 24

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

ER -