Pro-apoptotic protein kinase Cδ is associated with intranuclear inclusions in a transgenic model of Huntington's disease: PKCδ and htt-inclusions in HD mouse

In order to investigate any effect of truncated mutant huntingtin (tNhtt) aggregation on protein kinase C (PKC) signaling in Huntington's disease (HD), we studied a possible association of PKC isoforms with the aggregates using cellular and transgenic models of HD. In this report we describe an association of mutant tNhtt with at least three PKC isoforms (alpha, delta, zeta), as revealed by co-immunoprecipitation assays and immunocytochemistry in a cellular model of HD (Neuro2a cells expressing tNhtt-150Q-EGFP), as well as a specific association of PKCdelta with intranuclear aggregates in a transgenic model (R6/2 mice). Immunoblot analysis of isolated nuclear fractions shows an elevation of nuclear PKCdelta in transgenic brain tissue. The observed elevation has a strong similarity with the apoptotic translocation of PKCdelta detected in experiments with the mouse neuroblastoma Neuro2a cells. Using a Neuro2a cell line expressing tNhtt with the nuclear localization signal, we demonstrate the association of PKCdelta with intranuclear aggregates and present evidence that accumulation of PKCdelta in cell nuclei does not depend on mutant htt nuclear translocation. Our results suggest that the association of PKCdelta with intranuclear htt-aggregates may affect its apoptotic function in a transgenic model of HD.