Leitges Michael, Kovac Judit, Plomann Markus, Linden David J
Max-Planck-Institut für Experimentelle Endokrinologie, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.
Neuron. 2004 Nov 18;44(4):585-94. doi: 10.1016/j.neuron.2004.10.024.
Induction of cerebellar long-term depression (LTD) requires a postsynaptic cascade involving activation of mGluR1 and protein kinase C (PKC). Our understanding of this process has been limited by the fact that PKC is a large family of molecules, many isoforms of which are expressed in the relevant postsynaptic compartment, the cerebellar Purkinje cell. Here, we report that LTD is absent in Purkinje cells in which the alpha isoform of PKC has been reduced by targeted RNA interference or in cells derived from PKCalpha null mice. In both of these cases, LTD could be rescued by expression of PKCalpha but not other PKC isoforms. The special role of PKCalpha in cerebellar LTD is likely to derive from its unique PDZ ligand (QSAV). When this motif is mutated, PKCalpha no longer supports LTD. Conversely, when this PDZ ligand is inserted in a nonpermissive isoform, PKCgamma, it confers the capacity for LTD induction.
小脑长时程抑制（LTD）的诱导需要一个涉及代谢型谷氨酸受体1（mGluR1）激活和蛋白激酶C（PKC）的突触后级联反应。我们对这一过程的理解受到以下事实的限制：PKC是一个庞大的分子家族，其中许多亚型在相关的突触后区域即小脑浦肯野细胞中表达。在此，我们报告，通过靶向RNA干扰使PKC的α亚型减少的浦肯野细胞，或来自PKCα基因敲除小鼠的细胞中不存在LTD。在这两种情况下，LTD都可以通过PKCα的表达而不是其他PKC亚型的表达来挽救。PKCα在小脑LTD中的特殊作用可能源于其独特的PDZ配体（QSAV）。当这个基序发生突变时，PKCα不再支持LTD。相反，当这个PDZ配体插入到一个不支持LTD的亚型PKCγ中时，它赋予了诱导LTD的能力。
