PMID- 21607293
OWN - NLM
STAT- MEDLINE
DCOM- 20120325
LR  - 20211203
IS  - 1528-3658 (Electronic)
IS  - 1076-1551 (Print)
IS  - 1076-1551 (Linking)
VI  - 17
IP  - 9-10
DP  - 2011 Sep-Oct
TI  - Deptor knockdown enhances mTOR Activity and protein synthesis in myocytes and 
      ameliorates disuse muscle atrophy.
PG  - 925-36
LID - 10.2119/molmed.2011.00070 [doi]
AB  - Deptor is an mTOR binding protein that affects cell metabolism. We hypothesized 
      that knockdown (KD) of Deptor in C2C12 myocytes will increase protein synthesis 
      via stimulating mTOR-S6K1 signaling. Deptor KD was achieved using lentiviral 
      particles containing short hairpin (sh)RNA targeting the mouse Deptor mRNA 
      sequence, and control cells were transfected with a scrambled control shRNA. KD 
      reduced Deptor mRNA and protein content by 90%, which increased phosphorylation 
      of mTOR kinase substrates, 4E-BP1 and S6K1, and concomitantly increased protein 
      synthesis. Deptor KD myoblasts were both larger in diameter and exhibited an 
      increased mean cell volume. Deptor KD increased the percentage of cells in the S 
      phase, coincident with an increased phosphorylation (S807/S811) of retinoblastoma 
      protein (pRb) that is critical for the G(1) to S phase transition. Deptor KD did 
      not appear to alter basal apoptosis or autophagy, as evidenced by the lack of 
      change for cleaved caspase-3 and light chain (LC)3B, respectively. Deptor KD 
      increased proliferation rate and enhanced myotube formation. Finally, in vivo 
      Deptor KD (~50% reduction) by electroporation into gastrocnemius of C57/BL6 mice 
      did not alter weight or protein synthesis in control muscle. However, Deptor KD 
      prevented atrophy produced by 3 d of hindlimb immobilization, at least in part by 
      increasing protein synthesis. Thus, our data support the hypothesis that Deptor 
      is an important regulator of protein metabolism in myocytes and demonstrate that 
      decreasing Deptor expression in vivo is sufficient to ameliorate muscle atrophy.
FAU - Kazi, Abid A
AU  - Kazi AA
AD  - Department of Cellular and Molecular Physiology, Pennsylvania State University 
      College of Medicine, Hershey, Pennsylvania, USA.
FAU - Hong-Brown, Ly
AU  - Hong-Brown L
FAU - Lang, Susan M
AU  - Lang SM
FAU - Lang, Charles H
AU  - Lang CH
LA  - eng
GR  - GM38032/GM/NIGMS NIH HHS/United States
GR  - R01 AA011290/AA/NIAAA NIH HHS/United States
GR  - R37 AA011290/AA/NIAAA NIH HHS/United States
GR  - AA11290/AA/NIAAA NIH HHS/United States
GR  - R01 GM038032/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110519
PL  - England
TA  - Mol Med
JT  - Molecular medicine (Cambridge, Mass.)
JID - 9501023
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Eif4ebp1 protein, mouse)
RN  - 0 (Eukaryotic Initiation Factors)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (deptor protein, mouse)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 90-kDa)
RN  - EC 2.7.11.1 (Rps6ka1 protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Carrier Proteins/metabolism
MH  - Cell Cycle Proteins
MH  - Cell Line
MH  - Cell Proliferation
MH  - Cell Size
MH  - Eukaryotic Initiation Factors
MH  - Female
MH  - HEK293 Cells
MH  - Hindlimb Suspension
MH  - Humans
MH  - Immunoblotting
MH  - Intracellular Signaling Peptides and Proteins/genetics/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Muscle Cells/cytology/*metabolism
MH  - Muscle, Skeletal/growth & development/metabolism
MH  - Muscular Dystrophy, Animal/genetics/*metabolism/pathology
MH  - Myoblasts/cytology/metabolism
MH  - Organ Size
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation
MH  - *Protein Biosynthesis
MH  - *RNA Interference
MH  - Retinoblastoma Protein/metabolism
MH  - Ribosomal Protein S6 Kinases, 90-kDa/metabolism
MH  - S Phase
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
PMC - PMC3188866
EDAT- 2011/05/25 06:00
MHDA- 2012/03/27 06:00
PMCR- 2011/05/19
CRDT- 2011/05/25 06:00
PHST- 2011/02/21 00:00 [received]
PHST- 2011/05/18 00:00 [accepted]
PHST- 2011/05/25 06:00 [entrez]
PHST- 2011/05/25 06:00 [pubmed]
PHST- 2012/03/27 06:00 [medline]
PHST- 2011/05/19 00:00 [pmc-release]
AID - molmed.2011.00070 [pii]
AID - 11_70_kazi [pii]
AID - 10.2119/molmed.2011.00070 [doi]
PST - ppublish
SO  - Mol Med. 2011 Sep-Oct;17(9-10):925-36. doi: 10.2119/molmed.2011.00070. Epub 2011 
      May 19.