PMID- 19530170
OWN - NLM
STAT- MEDLINE
DCOM- 20091117
LR  - 20220309
IS  - 1097-4547 (Electronic)
IS  - 0360-4012 (Print)
IS  - 0360-4012 (Linking)
VI  - 87
IP  - 14
DP  - 2009 Nov 1
TI  - Lipid raft-targeted Akt promotes axonal branching and growth cone expansion via 
      mTOR and Rac1, respectively.
PG  - 3033-42
LID - 10.1002/jnr.22140 [doi]
AB  - The molecular mechanisms by which extracellular guidance cues regulate axonal 
      morphology are not fully understood. Recent findings suggest that increased 
      activity of the protein kinase Akt promotes dendritic branching and elongation in 
      hippocampal neurons. We tested whether expression of constitutively active Akt 
      (CA-Akt) in primary sensory neurons would promote axonal branching and whether 
      targeting CA-Akt to lipid rafts, common sites of Akt function, would 
      differentially regulate axonal morphology. Biolistic transduction of sensory 
      neurons induced a rapid expression of CA-Akt, resulting in increased axonal 
      branching, cell hypertrophy, and growth cone expansion. Additionally, we found 
      that targeting of CA-Akt to lipid rafts significantly potentiated growth cone 
      expansion compared with expression of CA-Akt throughout the neuron. Because lipid 
      rafts are concentrated within the growth cone, this finding suggests that 
      signaling of expansion is likely regulated locally. We found that CA-Akt-mediated 
      growth cone expansion, but not axonal branching, was attenuated by coexpression 
      of dominant-negative Rac1. In contrast, blockade of mammalian target of rapamycin 
      (mTOR) prevented axonal branching and hypertrophy in response to CA-Akt, but not 
      growth cone expansion. These data indicate that Akt activity can regulate growth 
      cone expansion via localized Rac1 signaling and regulate axonal branching and 
      soma size via activation of mTOR.
CI  - (c) 2009 Wiley-Liss, Inc.
FAU - Grider, M H
AU  - Grider MH
AD  - Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, 
      USA.
FAU - Park, D
AU  - Park D
FAU - Spencer, D M
AU  - Spencer DM
FAU - Shine, H D
AU  - Shine HD
LA  - eng
GR  - R01 NS039198/NS/NINDS NIH HHS/United States
GR  - T32 HL092332/HL/NHLBI NIH HHS/United States
GR  - NS39198/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
SB  - IM
MH  - Animals
MH  - Axons/metabolism
MH  - Blotting, Western
MH  - Chick Embryo
MH  - Growth Cones/*metabolism
MH  - Immunohistochemistry
MH  - Membrane Microdomains/*metabolism
MH  - Microscopy, Confocal
MH  - Nerve Regeneration/physiology
MH  - Protein Kinases/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-akt/genetics/*metabolism
MH  - TOR Serine-Threonine Kinases
MH  - Transduction, Genetic
MH  - rac1 GTP-Binding Protein/genetics/*metabolism
PMC - PMC6561343
MID - NIHMS968924
EDAT- 2009/06/17 09:00
MHDA- 2009/11/18 06:00
PMCR- 2019/06/12
CRDT- 2009/06/17 09:00
PHST- 2009/06/17 09:00 [entrez]
PHST- 2009/06/17 09:00 [pubmed]
PHST- 2009/11/18 06:00 [medline]
PHST- 2019/06/12 00:00 [pmc-release]
AID - 10.1002/jnr.22140 [doi]
PST - ppublish
SO  - J Neurosci Res. 2009 Nov 1;87(14):3033-42. doi: 10.1002/jnr.22140.