51. Loss of aPKCλ in differentiated neurons disrupts the polarity complex but does not induce obvious neuronal loss or disorientation in mouse brains
- Author
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Tomonori Hirose, Kazunori Akimoto, Masaru Kurosawa, Nobutaka Hattori, Shigeo Ohno, Tomoyuki Yamanaka, Nobuyuki Nukina, and Asako Tosaki
- Subjects
Male ,Cerebellum ,Mouse ,Cellular differentiation ,Hippocampus ,lcsh:Medicine ,Cell Cycle Proteins ,Neural Homeostasis ,Immunoenzyme Techniques ,Mice ,Molecular Cell Biology ,Neurobiology of Disease and Regeneration ,Cell polarity ,lcsh:Science ,Protein Kinase C ,Mice, Knockout ,Neurons ,Multidisciplinary ,Neuronal Morphology ,Reverse Transcriptase Polymerase Chain Reaction ,Cell adhesion molecule ,Neurogenesis ,Brain ,Cell Polarity ,Gene targeting ,Cell Differentiation ,Animal Models ,Cellular Structures ,Cell biology ,Isoenzymes ,medicine.anatomical_structure ,Female ,Cellular Types ,Research Article ,Histology ,Blotting, Western ,Central nervous system ,Biology ,Real-Time Polymerase Chain Reaction ,Signaling Pathways ,Model Organisms ,Developmental Neuroscience ,medicine ,Animals ,Immunoprecipitation ,RNA, Messenger ,Adaptor Proteins, Signal Transducing ,Glycoproteins ,Integrases ,lcsh:R ,Molecular biology ,Mice, Inbred C57BL ,Cellular Neuroscience ,lcsh:Q ,Molecular Neuroscience ,Cell Adhesion Molecules ,Neuroscience - Abstract
Cell polarity plays a critical role in neuronal differentiation during development of the central nervous system (CNS). Recent studies have established the significance of atypical protein kinase C (aPKC) and its interacting partners, which include PAR-3, PAR-6 and Lgl, in regulating cell polarization during neuronal differentiation. However, their roles in neuronal maintenance after CNS development remain unclear. Here we performed conditional deletion of aPKCλ, a major aPKC isoform in the brain, in differentiated neurons of mice by camk2a-cre or synapsinI-cre mediated gene targeting. We found significant reduction of aPKCλ and total aPKCs in the adult mouse brains. The aPKCλ deletion also reduced PAR-6β, possibly by its destabilization, whereas expression of other related proteins such as PAR-3 and Lgl-1 was unaffected. Biochemical analyses suggested that a significant fraction of aPKCλ formed a protein complex with PAR-6β and Lgl-1 in the brain lysates, which was disrupted by the aPKCλ deletion. Notably, the aPKCλ deletion mice did not show apparent cell loss/degeneration in the brain. In addition, neuronal orientation/distribution seemed to be unaffected. Thus, despite the polarity complex disruption, neuronal deletion of aPKCλ does not induce obvious cell loss or disorientation in mouse brains after cell differentiation.
- Published
- 2013