Activity- and mTOR-dependent suppression of Kv1.1 channel mRNA translation in dendrites.
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.
Raab-Graham
Kimberly F
KF
Howard Hughes Medical Institute, Departments of Physiology and Biochemistry, University of California, San Francisco, CA 94158, USA.
Haddick
Patrick C G
PC
Jan
Yuh Nung
YN
Jan
Lily Yeh
LY
D020413:3' Untranslated Regions; D000818:Animals; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D051662:Kv1.1 Potassium Channel / Q000096:biosynthesis* / Q000235:genetics*; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D014176:Protein Biosynthesis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012845:Sindbis Virus / Q000502:physiology; D020123:Sirolimus / Q000494:pharmacology; D013569:Synapses / Q000502:physiology; D058570:TOR Serine-Threonine Kinases
D020413:3' Untranslated Regions; C489293:Kcna1 protein, rat; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D011993:Recombinant Fusion Proteins; D051662:Kv1.1 Potassium Channel; D011494:Protein Kinases; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus