TY - JOUR
T1 - A unique PDZ ligand in PKCα confers induction of cerebellar long-term synaptic depression
AU - Leitges, Michael
AU - Kovac, Judit
AU - Plomann, Markus
AU - Linden, David J.
N1 - Funding Information:
Thanks to R. Bock and U. Braun for skillful technical assistance and to J. Steinberg and S. Gardner for helpful comments. This work was supported by the Max Planck Society (M.L.) and USPHS MH51106 and MH01590 (D.J.L.) and the Develbiss Fund (D.J.L.).
PY - 2004/11/18
Y1 - 2004/11/18
N2 - 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 α isoform of PKC has been reduced by targeted RNA interference or in cells derived from PKCα null mice. In both of these cases, LTD could be rescued by expression of PKCα but not other PKC isoforms. The special role of PKCα in cerebellar LTD is likely to derive from its unique PDZ ligand (QSAV). When this motif is mutated, PKCα no longer supports LTD. Conversely, when this PDZ ligand is inserted in a nonpermissive isoform, PKCγ, it confers the capacity for LTD induction.
AB - 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 α isoform of PKC has been reduced by targeted RNA interference or in cells derived from PKCα null mice. In both of these cases, LTD could be rescued by expression of PKCα but not other PKC isoforms. The special role of PKCα in cerebellar LTD is likely to derive from its unique PDZ ligand (QSAV). When this motif is mutated, PKCα no longer supports LTD. Conversely, when this PDZ ligand is inserted in a nonpermissive isoform, PKCγ, it confers the capacity for LTD induction.
UR - http://www.scopus.com/inward/record.url?scp=8844236296&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=8844236296&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2004.10.024
DO - 10.1016/j.neuron.2004.10.024
M3 - Article
C2 - 15541307
AN - SCOPUS:8844236296
SN - 0896-6273
VL - 44
SP - 585
EP - 594
JO - Neuron
JF - Neuron
IS - 4
ER -