title: Loss of aPKCλ in differentiated neurons disrupts the polarity complex but does not induce obvious neuronal loss or disorientation in mouse brains.
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.
authors.affiliation: Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, Saitama, Japan ; Department of Neuroscience for Neurodegenerative Disorders, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yamanaka
authors.affiliation: Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, Saitama, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Tosaki
authors.affiliation: Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, Saitama, Japan ; Department of Neuroscience for Neurodegenerative Disorders, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Kurosawa
authors.affiliation: Department of Molecular Medical Science, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Akimoto
authors.affiliation: Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, Yokohama, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Hirose
authors.affiliation: Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, Yokohama, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohno
authors.affiliation: Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
authors.affiliation: Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, Saitama, Japan ; Department of Neuroscience for Neurodegenerative Disorders, Juntendo University Graduate School of Medicine, Tokyo, Japan ; Core Research for Evolutionary Science and Technology, Japan Science and Technology Agency, Tokyo, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Nukina
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D016764:Cell Polarity; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D019426:Integrases / Q000378:metabolism; D007527:Isoenzymes / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D011493:Protein Kinase C / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099293:Protein Kinase C-lambda
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D006023:Glycoproteins; D019426:Integrases; D007527:Isoenzymes; D011493:Protein Kinase C; D012333:RNA, Messenger; D000099293:Protein Kinase C-lambda; C524369:LGL1 protein, mouse; C518597:Par6 protein, mouse; C115084:Pard3 protein, mouse; C045073:Cre recombinase