Protein kinase Cgamma is a signaling molecule required for the developmental speeding of alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor kinetics.
A key step in the maturation of glutamate synapses is the developmental speeding of alpha-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)gamma is necessary for the developmental speeding of AMPA-R kinetics. Targeted knockdown of PKCgamma with an antisense morpholino oligonucleotide [PKCgamma-morpholino (PKCgamma-MO)], prevents the normal speeding up of AMPA-R kinetics in Mauthner cells. PKCgamma-MO-injected embryos are incapable of trafficking AMPA-Rs following application of phorbol 12-myristate 13-acetate or PKCgamma. PKCgamma-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 PKCgamma-dependent trafficking of fast AMPA-Rs to synapses. Our findings reveal that PKCgamma is a molecular link underlying the developmental speeding of AMPA-Rs in zebrafish Mauthner cells.
Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
Shunmoogum A
SA
Patten
Birbickram
B
Roy
Marcus E
ME
Cunningham
James L
JL
Stafford
Declan W
DW
Ali
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D002491:Central Nervous System Agents / Q000494:pharmacology; D004625:Embryo, Nonmammalian / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials; D055785:Gene Knockdown Techniques; D007150:Immunohistochemistry; D007700:Kinetics; D016202:N-Methylaspartate / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D018091:Receptors, AMPA / Q000378:metabolism*; D012249:Rhombencephalon / Q000187:drug effects / Q000196:embryology* / Q000502:physiology*; D015398:Signal Transduction; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D015027:Zebrafish / Q000196:embryology
D002491:Central Nervous System Agents; D018091:Receptors, AMPA; C016658:phorbolol myristate acetate; D016202:N-Methylaspartate; C087857:protein kinase C gamma; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium