title: Transient translocation of conventional protein kinase C isoforms and persistent downregulation of atypical protein kinase Mzeta in long-term depression.
abstract: 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 Mzeta (PKMzeta), the autonomously active form of the atypical PKCzeta 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 CA1 region of hippocampal slices, conventional Ca(2+)/lipid-dependent PKC isoforms translocate from the cytosol to the membrane. This translocation was transient, lasting less than 15 min. In contrast, PKMzeta 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.
authors.affiliation: Laboratory of Molecular Neuroscience, Department of Physiology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Box 29, Brooklyn, NY 11203, USA.
authors.forename: S
authors.initials: S
authors.lastname: Hrabetova
authors.forename: T C
authors.initials: TC
authors.lastname: Sacktor
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015536:Down-Regulation; D006624:Hippocampus / Q000201:enzymology; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D009473:Neuronal Plasticity; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000099221:Protein Kinase C zeta
chemical_list: D007527:Isoenzymes; D011493:Protein Kinase C; D000099221:Protein Kinase C zeta