PMID- 31001086
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 13
DP  - 2019
TI  - mTORC1 Signaling Is Palmitoylation-Dependent in Hippocampal Neurons and 
      Non-neuronal Cells and Involves Dynamic Palmitoylation of LAMTOR1 and mTOR.
PG  - 115
LID - 10.3389/fncel.2019.00115 [doi]
LID - 115
AB  - The mechanistic target of rapamycin (mTOR) Complex 1 (mTORC1) controls growth and 
      proliferation of non-neuronal cells, while during neuronal development mTORC1 
      responds to glutamate and neurotrophins to promote neuronal migration and 
      dendritic arborization. Recent studies reveal that mTORC1 signaling complexes are 
      assembled on lysosomal membranes, but how mTORC1 membrane targeting is regulated 
      is not fully clear. Our examination of palmitoyl-proteomic databases and 
      additional bioinformatic analyses revealed that several mTORC1 proteins are 
      predicted to undergo covalent modification with the lipid palmitate. This 
      process, palmitoylation, can dynamically target proteins to specific membranes 
      but its roles in mTORC1 signaling are not well described. Strikingly, we found 
      that acute pharmacological inhibition of palmitoylation prevents amino 
      acid-dependent mTORC1 activation in HEK293T cells and brain-derived neurotrophic 
      factor (BDNF)-dependent mTORC1 activation in hippocampal neurons. We sought to 
      define the molecular basis for this finding and found that the mTORC1 proteins 
      LAMTOR1 and mTOR itself are directly palmitoylated, while several other mTORC1 
      proteins are not palmitoylated, despite strong bioinformatic prediction. 
      Interestingly, palmitoylation of LAMTOR1, whose anchoring on lysosomal membranes 
      is important for mTORC1 signaling, was rapidly increased prior to mTORC1 
      activation. In contrast, mTOR palmitoylation was decreased by stimuli that 
      activate mTORC1. These findings reveal that specific key components of the mTOR 
      pathway are dynamically palmitoylated, suggesting that palmitoylation is not 
      merely permissive for mTOR activation but is instead actively involved in 
      mTORC1-dependent signaling.
FAU - Sanders, Shaun S
AU  - Sanders SS
AD  - Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine at 
      Temple University, Philadelphia, PA, United States.
FAU - De Simone, Francesca I
AU  - De Simone FI
AD  - Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine at 
      Temple University, Philadelphia, PA, United States.
FAU - Thomas, Gareth M
AU  - Thomas GM
AD  - Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine at 
      Temple University, Philadelphia, PA, United States.
AD  - Department of Anatomy and Cell Biology, Lewis Katz School of Medicine at Temple 
      University, Philadelphia, PA, United States.
LA  - eng
PT  - Journal Article
DEP - 20190402
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC6454084
OTO - NOTNLM
OT  - BDNF
OT  - LAMTOR1
OT  - mTOR
OT  - mTORC1
OT  - neurotrophins
OT  - palmitoylation
EDAT- 2019/04/20 06:00
MHDA- 2019/04/20 06:01
PMCR- 2019/01/01
CRDT- 2019/04/20 06:00
PHST- 2018/10/31 00:00 [received]
PHST- 2019/03/08 00:00 [accepted]
PHST- 2019/04/20 06:00 [entrez]
PHST- 2019/04/20 06:00 [pubmed]
PHST- 2019/04/20 06:01 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2019.00115 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2019 Apr 2;13:115. doi: 10.3389/fncel.2019.00115. 
      eCollection 2019.