Activity- and mTOR-Dependent Suppression of Kv1.1 Channel mRNA Translation in Dendrites

• Published in: Science (American Association for the Advancement of Science) Vol. 314; no. 5796; pp. 144 - 148
• Main Authors: Raab-Graham, Kimberly F, Haddick, Patrick C.G, Jan, Yuh Nung, Jan, Lily Yeh
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 06-10-2006; The American Association for the Advancement of Science
• Subjects: 3' Untranslated Regions; Animals; Biological and medical sciences; Cells, Cultured; Dendrites; Dendrites - drug effects; Dendrites - metabolism; Excitatory Postsynaptic Potentials; Fluorescence; Fundamental and applied biological sciences. Psychology; Hippocampus - drug effects; Hippocampus - metabolism; In Vitro Techniques; Inhibitor drugs; Isolated neuron and nerve. Neuroglia; Kv1.1 Potassium Channel - biosynthesis; Kv1.1 Potassium Channel - genetics; Long term potentiation; Messenger RNA; N methyl D aspartate receptors; Neuronal Plasticity; Neurons; Neurons - metabolism; Neurons - virology; Neuroscience; Neurosciences; Oligonucleotide Array Sequence Analysis; Phosphorylation; Physiological regulation; Potassium; Protein Biosynthesis; Protein Kinase Inhibitors - pharmacology; Protein Kinases - physiology; Proteins; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - metabolism; Recombinant Fusion Proteins - metabolism; Ribonucleic acid; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sindbis Virus - physiology; Sirolimus - pharmacology; Synapses - physiology; Three prime untranslated regions; TOR Serine-Threonine Kinases; Vertebrates: nervous system and sense organs; Suppression; Central nervous system; Ionic channel; Protein; Encephalon; Dendrite; Surface; Vertebrata; Mammalia; Neuron; Synaptic plasticity; Voltage; NMDA; Inhibition; Potassium; Hippocampus
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1131693

Mammalian target of rapamycin (mTOR) is implicated in synaptic plasticity and local translation in dendrites. We found that the mTOR inhibitor, rapamycin, increased the Kv1.1 voltage-gated potassium channel protein in hippocampal neurons and promoted Kv1.1 surface expression on dendrites without altering its axonal expression. Moreover, endogenous Kv1.1 mRNA was detected in dendrites. Using Kv1.1 fused to the photoconvertible fluorescence protein Kaede as a reporter for local synthesis, we observed Kv1.1 synthesis in dendrites upon inhibition of mTOR or the N-methyl-D-aspartate (NMDA) glutamate receptor. Thus, synaptic excitation may cause local suppression of dendritic Kv1 channels by reducing their local synthesis.