Dataset Information

Comparative analysis of cholesterol sensitivity of Kir channels: role of the CD loop.

ABSTRACT: Kir channels are important in setting the resting membrane potential and modulating membrane excitability. A common feature of Kir2 channels and several other ion channels that has emerged in recent years is that they are regulated by cholesterol, a major lipid component of the plasma membrane whose excess is associated with multiple pathological conditions. Yet, the mechanism by which cholesterol affects channel function is not clear. We have recently shown that the sensitivity of Kir2 channels to cholesterol depends on residues in the CD loop of the cytosolic domain of the channels with one of the mutations, L222I, abrogating cholesterol sensitivity of the channels completely. Here we show that in addition to Kir2 channels, members of other Kir subfamilies are also regulated by cholesterol. Interestingly, while similarly to Kir2 channels, several Kir channels, Kir1.1, Kir4.1 and Kir6.2Delta36 were suppressed by an increase in membrane cholesterol, the function of Kir3.4* and Kir7.1 was enhanced following cholesterol enrichment. Furthermore, we show that independent of the impact of cholesterol on channel function, mutating residues in the corresponding positions of the CD loop in Kir2.1 and Kir3.4*, inhibits cholesterol sensitivity of Kir channels, thus extending the critical role of the CD loop beyond Kir2 channels.

SUBMITTER: Rosenhouse-Dantsker A

PROVIDER: S-EPMC2907253 | biostudies-literature | 2010 Jan-Feb

REPOSITORIES: biostudies-literature

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Comparative analysis of cholesterol sensitivity of Kir channels: role of the CD loop.

Rosenhouse-Dantsker Avia A Leal-Pinto Edgar E Logothetis Diomedes E DE Levitan Irena I

Channels (Austin, Tex.) 20100120 1

Kir channels are important in setting the resting membrane potential and modulating membrane excitability. A common feature of Kir2 channels and several other ion channels that has emerged in recent years is that they are regulated by cholesterol, a major lipid component of the plasma membrane whose excess is associated with multiple pathological conditions. Yet, the mechanism by which cholesterol affects channel function is not clear. We have recently shown that the sensitivity of Kir2 channels ...[more]

PMID: 19923917

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Project description:BackgroundMetal tolerance is often an integrative result of metal uptake and distribution, which are fine-tuned by a network of signaling cascades and metal transporters. Thus, with the goal of advancing the molecular understanding of such metal homeostatic mechanisms, comparative RNAseq-based transcriptome analysis was conducted to dissect differentially expressed genes (DEGs) in maize roots exposed to cadmium (Cd) stress.ResultsTo unveil conserved Cd-responsive genes in cereal plants, the obtained 5166 maize DEGs were compared with 2567 Cd-regulated orthologs in rice roots, and this comparison generated 880 universal Cd-responsive orthologs groups composed of 1074 maize DEGs and 981 rice counterparts. More importantly, most of the orthologous DEGs showed coordinated expression pattern between Cd-treated maize and rice, and these include one large orthologs group of pleiotropic drug resistance (PDR)-type ABC transporters, two clusters of amino acid transporters, and 3 blocks of multidrug and toxic compound extrusion (MATE) efflux family transporters, and 3 clusters of heavy metal-associated domain (HMAD) isoprenylated plant proteins (HIPPs), as well as all 4 groups of zinc/iron regulated transporter protein (ZIPs). Additionally, several blocks of tandem maize paralogs, such as germin-like proteins (GLPs), phenylalanine ammonia-lyases (PALs) and several enzymes involved in JA biosynthesis, displayed consistent co-expression pattern under Cd stress. Out of the 1074 maize DEGs, approximately 30 maize Cd-responsive genes such as ZmHIPP27, stress-responsive NAC transcription factor (ZmSNAC1) and 9-cis-epoxycarotenoid dioxygenase (NCED, vp14) were also common stress-responsive genes reported to be uniformly regulated by multiple abiotic stresses. Moreover, the aforementioned three promising Cd-upregulated genes with rice counterparts were identified to be novel Cd-responsive genes in maize. Meanwhile, one maize glutamate decarboxylase (ZmGAD1) with Cd co-modulated rice ortholog was selected for further analysis of Cd tolerance via heterologous expression, and the results suggest that ZmGAD1 can confer Cd tolerance in yeast and tobacco leaves.ConclusionsThese novel findings revealed the conserved function of Cd-responsive orthologs and paralogs, which would be valuable for elucidating the genetic basis of the plant response to Cd stress and unraveling Cd tolerance genes.

Dataset Information

Comparative analysis of cholesterol sensitivity of Kir channels: role of the CD loop.

Publications

Comparative analysis of cholesterol sensitivity of Kir channels: role of the CD loop.

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