title: Rictor regulates phosphorylation of the novel protein kinase C Apl II in Aplysia sensory neurons.
abstract: Rapamycin-insensitive companion of TOR (Rictor) is a conserved component of target of rapamycin complex 2 (TORC2), a complex implicated in phosphorylation of a number of signal transduction-related kinases, including protein kinase Cs (PKCs) at their 'hydrophobic' site in the carboxy-terminal extension domain. In the marine mollusk, Aplysia californica, an increase in phosphorylation of the novel PKC, Apl II, at the hydrophobic site is associated with a protein synthesis-dependent increase in synaptic strength seen after continuous application of serotonin. To determine if Rictor plays a role in this increase, we cloned the Aplysia ortholog of Rictor (ApRictor). An siRNA-mediated decrease in ApRictor levels in Aplysia sensory neurons led to a decrease in the phosphorylation of PKC Apl II at the hydrophobic site suggesting a role for ApRictor in hydrophobic site phosphorylation. However, over-expression of ApRictor was not sufficient to increase phosphorylation of PKC Apl II. Continuous application of serotonin increased phosphorylation of PKC Apl II at the hydrophobic site in cultured sensory neurons, and this was blocked by Torin, which inhibits both TORC1 and TORC2. Over-expression of ApRictor did not lead to change in the magnitude of serotonin-mediated phosphorylation, but did lead to a small increase in the membrane localization of phosphorylated PKC Apl II. In conclusion, these studies implicate Rictor in phosphorylation of a novel PKC during synaptic plasticity and suggest an additional role for Rictor in regulating the localization of PKCs.
authors: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors: Margaret
authors: M
authors: Labban
authors: John R
authors: JR
authors: Dyer
authors: Wayne S
authors: WS
authors: Sossin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia / Q000201:enzymology* / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation / Q000235:genetics; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D011984:Sensory Receptor Cells / Q000201:enzymology / Q000378:metabolism*; D013569:Synapses / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C493245:CRTC2 protein, human; D002352:Carrier Proteins; D007527:Isoenzymes; C492571:RICTOR protein, human; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D014157:Transcription Factors; C121046:Apl II protein kinase C; D058570:TOR Serine-Threonine Kinases; D011493:Protein Kinase C