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

Raab‐Graham, Kimberly F.; Haddick, Patrick C.G.; Jan, Yuh Nung

doi:10.1126/science.1131693

Cited by 249 publications

(282 citation statements)

References 28 publications

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“…Our results are consistent with other recent findings showing that activity deprivation produces a decrease in the expression of Kv1.1 channels in hippocampal (Grosse et al, 2000;Raab-Graham et al, 2006) and auditory brainstem neurons (Lu et al, 2004). Studies examining homeostatic plasticity have primarily focused on measurements in individual neurons, yet given the fact that homeostasis can be a global event affecting all members in a network begs the question as to the network effect of homeostasis.…”

Section: Homeostatic Plasticity and Network Synchronysupporting

confidence: 82%

Spike-Time Precision and Network Synchrony Are Controlled by the Homeostatic Regulation of the D-Type Potassium Current

Cudmore¹,

Fronzaroli-Molinières²,

Giraud³

et al. 2010

J. Neurosci.

128

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Homeostatic plasticity of neuronal intrinsic excitability (HPIE) operates to maintain networks within physiological bounds in response to chronic changes in activity. Classically, this form of plasticity adjusts the output firing level of the neuron through the regulation of voltage-gated ion channels. Ion channels also determine spike timing in individual neurons by shaping subthreshold synaptic and intrinsic potentials. Thus, an intriguing hypothesis is that HPIE can also regulate network synchronization. We show here that the dendrotoxin-sensitive D-type K ϩ current (I D ) disrupts the precision of AP generation in CA3 pyramidal neurons and may, in turn, limit network synchronization. The reduced precision is mediated by the sequence of outward I D followed by inward Na ϩ current. The homeostatic downregulation of I D increases both spike-time precision and the propensity for synchronization in iteratively constructed networks in vitro. Thus, network synchronization is adjusted in area CA3 through activity-dependent remodeling of I D .

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Section: Homeostatic Plasticity and Network Synchronysupporting

confidence: 82%

Spike-Time Precision and Network Synchrony Are Controlled by the Homeostatic Regulation of the D-Type Potassium Current

Cudmore¹,

Fronzaroli-Molinières²,

Giraud³

et al. 2010

J. Neurosci.

128

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show abstract

“…45,46 Conversely, the translation of specific mRNAs can be actively inhibited by mTORC1 activity; one example is the translation of the voltage-gated potassium channel KV1.1. 47 Thus, while we can conclude that the global rates of ribosome activity are similar in chronically rapamycintreated and S6K1 −/− mice compared with controls, we cannot rule out subtle changes in translational activity on the level of specific mRNAs.…”

Section: Discussionmentioning

confidence: 99%

Chronic rapamycin treatment or lack ofS6K1does not reduce ribosome activity in vivo

et al. 2013

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reducing activity of the mtorC1/S6K1 pathway has been shown to extend lifespan in both vertebrate and invertebrate models. For instance, both pharmacological inhibition of mtorC1 with the drug rapamycin or S6K1 knockout extends lifespan in mice. Since studies with invertebrate models suggest that reducing translational activity can increase lifespan, we reasoned that the benefits of decreased mtorC1 or S6K1 activity might be due, at least in part, to a reduction of general translational activity. Here, we report that mice given a single dose of rapamycin have reduced translational activity, while mice receiving multiple injections of rapamycin over 4 weeks show no difference in translational activity compared with vehicle-injected controls. Furthermore, mice lacking S6K1 have no difference in global translational activity compared with wild-type littermates as measured by the percentage of ribosomes that are active in multiple tissues. translational activity is reduced in S6K1-knockout mice following single injection of rapamycin, demonstrating that rapamycin's effects on translation can occur independently of S6K1. taken together, these data suggest that benefits of chronic rapamycin treatment or lack of S6K1 are dissociable from potential benefits of reduced translational activity, instead pointing to a model whereby changes in translation of specific subsets of mrNas and/or translation-independent effects of reduced mtor signaling underlie the longevity benefits.

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“…shown to be predominantly localized to axons, Jan and colleagues designed a reporter with Kaede fused to the amino terminus of the potassium channel protein Kv1.1 and whose mRNA also contained the 3 0 UTR of Kv1.1 (Raab-Graham et al 2006). On photoconversion and rapamycin treatment, the investigators observed new Kaede-Kv1.1 expression in distal regions of the dendrites indicating that the 3 0 UTR contributes to the dendritic localization of the mRNA and subsequent stimulation-dependent translation of Kv1.1 (Fig.…”

Section: Single-cell Imagingmentioning

confidence: 99%

Imaging Translation in Single Cells Using Fluorescent Microscopy

Chao

Yoon

Singer

2012

Cold Spring Harbor Perspectives in Biology

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The regulation of translation provides a mechanism to control not only the abundance of proteins, but also the precise time and subcellular location that they are synthesized. Much of what is known concerning the molecular basis for translational control has been gleaned from experiments (e.g., luciferase assays and polysome analysis) that measure average changes in the protein synthesis of a population of cells, however, mechanistic insights can be obscured in ensemble measurements. The development of fluorescent microscopy techniques and reagents has allowed translation to be studied within its cellular context. Here we highlight recent methodologies that can be used to study global changes in protein synthesis or regulation of specific mRNAs in single cells. Imaging of translation has provided direct evidence for local translation of mRNAs at synapses in neurons and will become an important tool for studying translational control.

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

Cited by 249 publications

References 28 publications

Spike-Time Precision and Network Synchrony Are Controlled by the Homeostatic Regulation of the D-Type Potassium Current

Spike-Time Precision and Network Synchrony Are Controlled by the Homeostatic Regulation of the D-Type Potassium Current

Chronic rapamycin treatment or lack ofS6K1does not reduce ribosome activity in vivo

Imaging Translation in Single Cells Using Fluorescent Microscopy

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