PMID- 23569215
OWN - NLM
STAT- MEDLINE
DCOM- 20130611
LR  - 20220309
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 201
IP  - 2
DP  - 2013 Apr 15
TI  - Ablation of the mTORC2 component rictor in brain or Purkinje cells affects size 
      and neuron morphology.
PG  - 293-308
LID - 10.1083/jcb.201205030 [doi]
AB  - The mammalian target of rapamycin (mTOR) assembles into two distinct 
      multi-protein complexes called mTORC1 and mTORC2. Whereas mTORC1 is known to 
      regulate cell and organismal growth, the role of mTORC2 is less understood. We 
      describe two mouse lines that are devoid of the mTORC2 component rictor in the 
      entire central nervous system or in Purkinje cells. In both lines neurons were 
      smaller and their morphology and function were strongly affected. The phenotypes 
      were accompanied by loss of activation of Akt, PKC, and SGK1 without effects on 
      mTORC1 activity. The striking decrease in the activation and expression of 
      several PKC isoforms, the subsequent loss of activation of GAP-43 and MARCKS, and 
      the established role of PKCs in spinocerebellar ataxia and in shaping the actin 
      cytoskeleton strongly suggest that the morphological deficits observed in 
      rictor-deficient neurons are mediated by PKCs. Together our experiments show that 
      mTORC2 has a particularly important role in the brain and that it affects size, 
      morphology, and function of neurons.
FAU - Thomanetz, Venus
AU  - Thomanetz V
AD  - Biozentrum, University of Basel, CH-4056 Basel, Switzerland.
FAU - Angliker, Nico
AU  - Angliker N
FAU - Cloetta, Dimitri
AU  - Cloetta D
FAU - Lustenberger, Regula M
AU  - Lustenberger RM
FAU - Schweighauser, Manuel
AU  - Schweighauser M
FAU - Oliveri, Filippo
AU  - Oliveri F
FAU - Suzuki, Noboru
AU  - Suzuki N
FAU - Ruegg, Markus A
AU  - Ruegg MA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130408
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Carrier Proteins)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Rapamycin-Insensitive Companion of mTOR Protein)
RN  - 0 (rictor protein, mouse)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Brain/enzymology/*metabolism/pathology
MH  - Carrier Proteins/*metabolism
MH  - Cell Count
MH  - *Cell Shape
MH  - *Cell Size
MH  - Cerebellum/enzymology/pathology
MH  - Enzyme Activation
MH  - Gene Deletion
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Mechanistic Target of Rapamycin Complex 2
MH  - Mice
MH  - Mice, Knockout
MH  - Microcephaly/enzymology/pathology
MH  - Multiprotein Complexes/*metabolism
MH  - Phenotype
MH  - Purkinje Cells/enzymology/*metabolism/*pathology
MH  - Rapamycin-Insensitive Companion of mTOR Protein
MH  - Synapses/metabolism
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC3628512
EDAT- 2013/04/10 06:00
MHDA- 2013/06/12 06:00
PMCR- 2013/10/15
CRDT- 2013/04/10 06:00
PHST- 2013/04/10 06:00 [entrez]
PHST- 2013/04/10 06:00 [pubmed]
PHST- 2013/06/12 06:00 [medline]
PHST- 2013/10/15 00:00 [pmc-release]
AID - jcb.201205030 [pii]
AID - 201205030 [pii]
AID - 10.1083/jcb.201205030 [doi]
PST - ppublish
SO  - J Cell Biol. 2013 Apr 15;201(2):293-308. doi: 10.1083/jcb.201205030. Epub 2013 
      Apr 8.