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Review
. 2017 Apr:43:79-86.
doi: 10.1016/j.conb.2017.01.004. Epub 2017 Feb 1.

Biochemistry and neuroscience: the twain need to meet

Affiliations
Review

Biochemistry and neuroscience: the twain need to meet

Mary B Kennedy. Curr Opin Neurobiol. 2017 Apr.

Abstract

Neuroscience has come to mean the study of electrophysiology of neurons and synapses, micro and macro-scale neuroanatomy, and the functional organization of brain areas. The molecular axis of the field, as reflected in textbooks, often includes only descriptions of the structure and function of individual channels and receptor proteins, and the extracellular signals that guide development and repair. Studies of cytosolic 'molecular machines', large assemblies of proteins that orchestrate regulation of neuronal functions, have been neglected. However, a complete understanding of brain function that will enable new strategies for treatment of the most intractable neural disorders will require that in vitro biochemical studies of molecular machines be reintegrated into the field of neuroscience.

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Figures

Figure 1
Figure 1
In PKMζ null mutant mice, PKCι/λ compensates for the normal function of PKMζ. A) In Wild-type mice, tetanization increases the amount of PKMζ at 3 hrs after stimulus, but does not increase the amount or phosphorylation of PKCι/λ. In PKMζ null mice, tetanization increases the amount of PKCι/λ and its phosphorylated form. B) Maintenance of late phase LTP in hippocampal slices from PKMζ null mice (filled circles) is reversed by application of the PKCι/λ antagonist, ICAP (10 μM) when it is applied 3 hrs post tetanus. Tetanus was applied at the time indicated by the arrow. The inset shows representative extracellular recorded EPSPs (field Excitatory PostSynaptic Potentials) at the time points indicated by small numbers. C) ICAP has no effect on maintenance of late LTP in wild type hippocampal slices (filled circles). As expected, inhibition of PKCι/λ by ICAP blocks induction of LTP in a second pathway in the same wild type slice (open circles). This control shows that the inhibitor is working. The inset on the right is an additional control showing that, in the absence of ICAP, LTP can be induced in a second pathway by tetanization after 270 min of incubation of the slice. Reproduced from Tsokas et al. eLife 2016;5:e14846. DOI: 10.7554/eLife.14846 [23]
Figure 2
Figure 2
Activation of CaMKII by NMDA receptors causes synGAPα1 and synGAPα2 to move away from the postsynaptic membrane. SynGAP moves into the periphery of the PSD, which the authors refer to as the “pallium.” Hippocampal cultures were fixed and stained by immunogold-labeling for the isoform of synGAP that contains a PDZ ligand (α1) and the isoform that does not (α2). A) Control labeling; B) Cultures were incubated with tatCN21, an inhibitor of CaMKII; C) Cultures were exposed to 50 μM NMDA for 2 min; D) Cultures were treated with NMDA and a control, scrambled peptide that does not inhibit CaMKII (tatCtrl); E) Cultures were treated with NMDA and tatCN21. Reproduced from Yang et al. (2013) PLoS ONE 8(8): e71795. doi:10.1371/journal.pone.0071795 [31].
Figure 3
Figure 3
Altered composition of the postsynaptic density in mice with heterozygous deletion of synGAP. In these experiments, postsynaptic densities were prepared by standard procedures from pooled brains of six synGAP heterozygous (HET) mice and six wild type (WT) litter mates. The ratios of amounts of each protein to the amount of PSD-95 in the two postsynaptic density preparations were determined from quantitative immunoblots scanned with a Li-Cor Odyssey scanner. Individual points (n) are technical replicates of the ratios determined from single lanes on sets of gels each containing six lanes of 5 μg wild type PSD and six lanes of 5μg synGAP HET PSD. A) Ratios of synGAP to PSD-95 in WT and HET. p = 0.0007; Cohen’s d (effect size) = 1.75. B) Ratios of TARPs to PSD-95 in WT and HET. p = 0.017, Cohen’s d = 0.93. C) Ratios of LRRTM2 to PSD-95 in WT and HET. p = 0.0035, Cohen’s d = 0.66. Reproduced from Walkup et al. eLife 2016;5:e16813. DOI: 10.7554/eLife.16813 [37].

References

    1. Alberts B. The cell as a collection of protein machines: preparing the next generation of molecular biologists. Cell. 1998;92:291–294. - PubMed
    1. He Y, Yan C, Fang J, Inouye C, Tjian R, Ivanov I, Nogales E. Near-atomic resolution visualization of human transcription promoter opening. Nature. 2016;533:359–365. - PMC - PubMed
    1. Lin DH, Stuwe T, Schilbach S, Rundlet EJ, Perriches T, Mobbs G, Fan Y, Thierbach K, Huber FM, Collins LN, et al. Architecture of the symmetric core of the nuclear pore. Science. 2016;352:aaf1015. - PMC - PubMed
    1. Dodonova SO, Diestelkoetter-Bachert P, von Appen A, Hagen WJ, Beck R, Beck M, Wieland F, Briggs JA. VESICULAR TRANSPORT.A structure of the COPI coat and the role of coat proteins in membrane vesicle assembly. Science. 2015;349:195–198. - PubMed
    1. Hyman AA, Weber CA, Julicher F. Liquid-liquid phase separation in biology. Annu Rev Cell Dev Biol. 2014;30:39–58. This review describes the molecular forces that underlie formation of membrane-less compartments such as the nucleolus, the centrosome, and, perhaps, the postsynaptic density. - PubMed

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