@Autonomous CaMKII mediates both LTP and LTD using a mechanism for differential substrate site selection (Coultrap et al. 2014)

2022-05-07: reference:

@Autonomous CaMKII mediates both LTP and LTD using a mechanism for differential substrate site selection (Coultrap et al. 2014) #

• Thr286 is one such site of CAMK autophosphorylation whereby it can become “autonomous”.
  • Thr286 phosphorylation is induced by LTP stimuli, and required for NMDAR-dependent LTP induction R. R Subsequently, LTD stimuli can induce phosphorylation of Ser567.
    • *Biochemical studies have shown that “autonomous” CAMK II is ∼5-fold further stimulated by Ca2+/Calmodulin.. even autonomous CaMKII activity must be further stimulated by Ca2+/CaM for enhancement of synaptic strength. R
      • Indeed, in inducing maximal conditions, Ca2+/Calmodulin enhances phosphorylation at Ser831, but not Ser567. Meanwhile, Ser567 was phosphorylated more readily than Ser831 by autonomous CaMK II in the absence of further stimulation (i.e. weak (but possibly prolonged) Ca2+, characteristic of LTD, while LTP is characterized by strong and brief Ca2+ currents.)
        • Both induce autophosphorylation at T286. I don’t think they differ there.
  • CaMKII Metaplasticity Drives Aβ Oligomer-Mediated Synaptotoxicity (Opazo et al. 2018)
    • Oligomeric Amyloid β prevents LTP from NR2B-containing NMDAR via promoting CAMK II activation, and prolonged misactivation leads to destabilization of surface AMPARs. Aβ prevents CAMK II’s autophosphorylation at T286. Idrk.
      • Indeed, Ifenprodil (NR2B antagonist) fully prevented APP-mediated activation of CAMKII.
      • What needs to be recalled here is that prolonged activation implies it is a weak signal or something; the above study states LTD stimulus is characterized as low, but persistent Ca2+ (and therefore calmodulin) activity, while LTP stimulus is characterized by high, quicky reversed Ca2+.