Transient translocation of conventional protein kinase C isoforms and persistent downregulation of atypical protein kinase Mζ in long-term depression
Transient translocation of conventional protein kinase C isoforms and persistent downregulation of atypical protein kinase Mζ in long-term depression
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DOI：
10.1016/s0169-328x(01)00185-1
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发表时间：
2001-11-01
期刊：
影响因子：
--
通讯作者：
Sacktor, TC
中科院分区：
文献类型：
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作者：
Hrabetova, S;Sacktor, TC
持续性去磷酸化与长期抑郁(LTD)的分子机制有关。去磷酸化可能是由于磷酸酶活性的持续增加或激酶活性的持续下降。我们以前已经发现蛋白激酶M Zeta(PKM Zeta)是非典型PKC Zeta同工酶的自主活性形式，它增加了长时程增强(LTP)：这与PKC降低磷酸化水平在LTD中很重要的假设是一致的。然而，最近，PKC的磷酸化增加也被认为与LTD有关。这些相互矛盾的结果可能部分是由于PKC的多种亚型，它们可能在LTD的不同阶段独立调节。我们现在发现，在45 S，在低频(3赫兹)：刺激诱导LTD在海马脑片CA1区，传统的钙/脂依赖的蛋白激酶C亚型从胞浆转移到膜。这种易位是短暂的，持续时间不到15分钟。相反，在LTD维持2小时后，PKM Zeta持续下降。因此，不同的PKC亚型的激活和下调可能参与了LTD的诱导和维持机制。(C)2001 Elsevier Science B.V.保留所有权利。
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.