Transient translocation of conventional protein kinase C isoforms and persistent downregulation of atypical protein kinase Mζ in long-term depression

Persistent dephosphorylation has been implicated in the molecular mechanisms of long-term depression (LTD). Dephosphorylation may be due to either a persistent increase in phosphatase activity or a persistent decrease in kinase activity. We have previously found that protein kinase M zeta (PKM zeta), the autonomously active form of the atypical PKC zeta isozyme that increases in long-term potentiation (LTP), decreases in LTD: This is consistent with the hypothesis that decreased levels of phosphorylation by PKC are important in LTD. Recently, however, increased phosphorylation by PKC has also been implicated in LTD. These contradictory results might be explained, in part, by the multiple isoforms of PKC, which may be independently regulated during the different phases of LTD. We now find that 45 s after low-frequency (3 Hz): stimulation that induces LTD in the CAI region of hippocampal slices, conventional Ca2+/lipid-dependent PKC isoforms translocate from the cytosol to the membrane. This, translocation was transient, lasting less than 15 min. In contrast, PKM zeta, was persistently decreased through 2 h of LTD maintenance. Therefore, the activation and downregulation of distinct PKC isoforms may participate in the induction and maintenance mechanisms of LTD. (C) 2001 Elsevier Science B.V. All rights reserved.