A unique PDZ ligand in PKCalpha confers induction of cerebellar long-term synaptic depression

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Animals
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Ligands
  • Long-Term Synaptic Depression / physiology*
  • Mice
  • Mitogen-Activated Protein Kinase Kinases
  • Patch-Clamp Techniques
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Protein Kinase C-alpha
  • Protein Serine-Threonine Kinases / metabolism
  • Purkinje Cells / enzymology*
  • Synapses / physiology
  • Transfection


  • Isoenzymes
  • Ligands
  • Protein Serine-Threonine Kinases
  • PRKCA protein, human
  • Prkca protein, mouse
  • Protein Kinase C
  • Protein Kinase C-alpha
  • Mitogen-Activated Protein Kinase Kinases
  • PDZ-binding kinase