title: PKMζ, but not PKCλ, is rapidly synthesized and degraded at the neuronal synapse.
abstract: Synthesizing, localizing, and stabilizing new protein copies at synapses are crucial factors in maintaining the synaptic changes required for storing long-term memories. PKMζ recently emerged as a molecule putatively responsible for maintaining encoded memories over time because its presence correlates with late LTP and because its inhibition disrupts LTP in vitro and long-term memory storage in vivo. Here we investigated PKMζ stability in rat neurons to better understand its role during information encoding and storage. We used TimeSTAMP reporters to track the synthesis and degradation of PKMζ as well as a related atypical PKC, PKCλ. These reporters revealed that both PKMζ and PKCλ were upregulated after chemical LTP induction; however, these new PKMζ copies exhibited more rapid turnover than basally produced PKMζ, particularly in dendritic spines. In contrast to PKMζ, new PKCλ copies exhibited elevated stability. Stable information storage over long periods of time is more challenging the shorter the metabolic lifetime of the candidate molecules.
authors.affiliation: Department of Pharmacology.
authors.forename: Sakina F
authors.identifier: http://orcid.org/0000-0001-8143-5839
authors.initials: SF
authors.lastname: Palida
authors.affiliation: Department of Pharmacology.
authors.forename: Margaret T
authors.identifier: http://orcid.org/0000-0001-8919-9359
authors.initials: MT
authors.lastname: Butko
authors.affiliation: Department of Pharmacology, Howard Hughes Medical Institute.
authors.forename: John T
authors.initials: JT
authors.lastname: Ngo
authors.affiliation: National Center for Microscopy and Imaging Research.
authors.forename: Mason R
authors.initials: MR
authors.lastname: Mackey
authors.affiliation: Department of Pharmacology, Howard Hughes Medical Institute.
authors.forename: Larry A
authors.identifier: http://orcid.org/0000-0001-7759-0430
authors.initials: LA
authors.lastname: Gross
authors.affiliation: National Center for Microscopy and Imaging Research, Department of Neurosciences, and.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Ellisman
authors.affiliation: Department of Pharmacology, Howard Hughes Medical Institute, Department of Chemistry & Biochemistry, University of California, San Diego, La Jolla, California 92093 rtsien@ucsd.edu.
authors.forename: Roger Y
authors.initials: RY
authors.lastname: Tsien
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000378:metabolism* / Q000502:physiology; D004795:Enzyme Stability; D057809:HEK293 Cells; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D017774:Long-Term Potentiation; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism* / Q000502:physiology; D015854:Up-Regulation; D000099293:Protein Kinase C-lambda; D000099221:Protein Kinase C zeta
chemical_list: D007527:Isoenzymes; D011493:Protein Kinase C; D000099293:Protein Kinase C-lambda; D000099221:Protein Kinase C zeta
keywords: long-term potentiation; memory; protein kinases; protein synthesis; protein turnover; synaptic plasticity