Protein kinase Cγ is a signaling molecule required for the developmental speeding of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor kinetics

Authors

  • Shunmoogum A. Patten,

    1. Department of Biological Sciences, Biological Sciences Building, University of Alberta, Edmonton, Alberta, Canada, T6G 2E9
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  • Birbickram Roy,

    1. Department of Biological Sciences, Biological Sciences Building, University of Alberta, Edmonton, Alberta, Canada, T6G 2E9
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  • Marcus E. Cunningham,

    1. Department of Biological Sciences, Biological Sciences Building, University of Alberta, Edmonton, Alberta, Canada, T6G 2E9
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  • James L. Stafford,

    1. Department of Biological Sciences, Biological Sciences Building, University of Alberta, Edmonton, Alberta, Canada, T6G 2E9
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  • Declan W. Ali

    1. Department of Biological Sciences, Biological Sciences Building, University of Alberta, Edmonton, Alberta, Canada, T6G 2E9
    2. Centre for Neuroscience, University of Alberta, 5005-A Katz Group – Rexall Centre, Edmonton, Alberta, Canada, T6G 2E1
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Dr Declan W. Ali, 1Department of Biological Sciences, as above.
E-mail: declan.ali@ualberta.ca

Abstract

A key step in the maturation of glutamate synapses is the developmental speeding of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPA-R) kinetics, which occurs via a switch in receptor subtypes. However, the molecular components required for the switch in receptors are unknown. Here, we used the zebrafish preparation to show that activation of protein kinase C (PKC)γ is necessary for the developmental speeding of AMPA-R kinetics. Targeted knockdown of PKCγ with an antisense morpholino oligonucleotide [PKCγ-morpholino (PKCγ-MO)], prevents the normal speeding up of AMPA-R kinetics in Mauthner cells. PKCγ-MO-injected embryos are incapable of trafficking AMPA-Rs following application of phorbol 12-myristate 13-acetate or PKCγ. PKCγ-MO-injected embryos do not hatch or exhibit the C-start escape response. Increasing synaptic activity (33 h post-fertilization embryos) by application of an elevated K+ medium or by application of N-methyl-d-aspartate induces rapid PKCγ-dependent trafficking of fast AMPA-Rs to synapses. Our findings reveal that PKCγ is a molecular link underlying the developmental speeding of AMPA-Rs in zebrafish Mauthner cells.

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