RNA editing in brain controls a determinant of ion flow in glutamate-gated channels

Sommer, Bernd; Köhler, Martin; Sprengel, Rolf; Seeburg, Peter H.

doi:10.1016/0092-8674(91)90568-j

Cited by 1,380 publications

(984 citation statements)

References 43 publications

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“…• ~' ~, 'P~+ "-:"k" of the putative channel forming segment TMII of GluR-5, .6 and GIuR-B [21]. The isolated eDNA clones of the GluR-7 subunit encoded a glutamine in this region, which corresponds to the unedited TMII form.…”

Section: Resultsmentioning

confidence: 99%

High‐affinity kainate a domoate receptors in rat brain

et al. 1992

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Section: Resultsmentioning

confidence: 99%

High‐affinity kainate a domoate receptors in rat brain

et al. 1992

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“…Primarily, these properties are conferred by the presence or absence of the GluA2 subunit. In the brain, the vast majority (>99%) of GluA2 mRNA exists in an edited form, resulting in a change from glutamine to arginine at position 607 150 . This alteration of charge, which occurs in the channel pore, blocks the passage of Ca 2+ ions, prevents the channel from being blocked by intracellular polyamines, and reduces the single-channel conductance of the receptor 151 .…”

Section: Boxesmentioning

confidence: 99%

Synaptic AMPA receptor composition in development, plasticity and disease

2016

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. PrefaceAMPARs are assemblies of four core subunits, GluA1-4, that mediate most fast excitatory neurotransmission. The component subunits determine the functional properties of AMPARs and the prevailing view is that the subunit composition also determines AMPAR trafficking, which is dynamically regulated during development, synaptic plasticity, and in response to neuronal stress in disease. Recently, the subunit-dependence of AMPAR trafficking has been questioned leading to a reappraisal of the field. Here we review what is known, uncertain, conjectured and unknown about the roles of individual subunits and how they impact on AMPAR assembly, trafficking and function under normal and pathological conditions. IntroductionAMPA receptors (AMPARs) are a subtype of ionotropic glutamate receptors that are the 'work-horses' of fast excitatory neurotransmission in the CNS. Developmentallyand activity-regulated changes in the numbers and properties of AMPARs localized at the postsynaptic membrane are essential for excitatory synapse formation, stabilization, synaptic plasticity and neural circuit formation. Consequently, the logistics of the delivery, retention and removal of individual AMPARs with defined subunit compositions at specific synapses is highly complex. A typical cortical or hippocampal pyramidal neuron contains on the order of 10,000 synapses and the AMPARs at each synapse are independently and dynamically regulated in response to developmental cues, synaptic activity and environmental stresses. Furthermore, defects in the processes that control AMPAR assembly, trafficking and synaptic expression are intimately linked to psychiatric and neurological conditions, and also with cognitive decline in neurodegenerative diseases. Remarkable progress has been achieved in understanding how AMPAR trafficking, is orchestrated by a large array of AMPAR interacting proteins. These studies have established a set of hierarchical subunit-specific rules that control AMPAR trafficking under basal and activity-dependent conditions. Furthermore, there has been a growing appreciation that subunit composition can tune the properties of AMPARs to specific conditions. Nonetheless, how AMPARs comprising different subunits are differentially trafficked to control synaptic development, stabilisation and plasticity is a key unanswered question. Here, we provide an overview of the current state of knowledge of subunit-specific AMPAR trafficking and outline what we believe to be the key unresolved questions in the field. 2 Subunit-specific traffickingMost AMPARs are heterotetrameric assemblies of combinations of the subunits GluA1, GluA2, GluA3 and GluA4. AMPARs are expressed in both neurons and glia throughout the CNS 1 and have a turnover time of between 10 hours and 2 days depending on the type of neuron and developmental stage 2,3 . Each subunit has an identical membrane topology and c...

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“…Besides the various forms of editing for RNAs encoded in the mitochondria of plants or kimetoplastid protozoa, two paradigms for mRNA editing of nuclear encoded genes have been described, editing of apolipoprotein (apo) B mRNA and editing of mRNAs for certain subunits of glutamate-gated cation channels (GluRs) (Powell et al, 1987;Sommer et al, 1991). Editing of GluR transcripts changes genomically encoded adenosines into inosines altering amino acid residues at functional important domains of the encoded ion channels (Mass et al, 1997).…”

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Absence of APOBEC-1 mediated mRNA editing in human carcinomas

et al. 1999

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The transgene expression of the catalytic subunit APOBEC-1 of the apo B mRNA editing enzymecomplex can cause hepatocellular carcinoma in mice and rabbits. It has been proposed that aberrant editing of mRNA may represent a novel oncogenic principle. This investigation aimed to de®ne whether such aberrant hyperediting mediated by APOBEC-1 occurs in human carcinomas. Editing and hyperediting of apo B, NAT1 or NF1 mRNA was not identi®ed in any of 28 resected tumor specimens, including hepatocellular, bile duct, gastric, colorectal, pancreatic adeno-and neuroendocrine, lung adeno-, medullary thyroid and breast carcinoma, soft tissue sarcoma and neuroblastoma. In most types of carcinoma, signi®cant levels for full-length APOBEC-1 mRNA could not be detected. Low level expression of APOBEC-1 was found in colorectal and gastric carcinoma where most of the APOBEC-1 mRNA is inactivated by alternate splicing. The`auxiliary' components of the apo B mRNA editing enzyme-complex are missing in many tumors including colorectal and gastric carcinoma, but are highly expressed in hepatocellular, lung adeno-and breast carcinoma all of which lack APOBEC-1. Taken together, either APOBEC-1 or the`auxiliary' components of the apo B mRNA editing enzyme-complex or both are missing in human carcinomas resulting in the absence of mRNA editing. Currently, there is no evidence that aberrant editing mediated by APOBEC-1 contributes to the tumorigenesis of natural human carcinomas.

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RNA editing in brain controls a determinant of ion flow in glutamate-gated channels

Cited by 1,380 publications

References 43 publications

High‐affinity kainate a domoate receptors in rat brain

High‐affinity kainate a domoate receptors in rat brain

Synaptic AMPA receptor composition in development, plasticity and disease

Absence of APOBEC-1 mediated mRNA editing in human carcinomas

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