Membrane microdomain determines the specificity of receptor-mediated modulation of Kv7/M potassium currents

Liu, Y.; Xu, Jiaxi; Zhang, F.; Liang, Haihua; Du, Xiaona; Zhang, H.

doi:10.1016/j.neuroscience.2013.08.064

Cited by 13 publications

(12 citation statements)

References 57 publications

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“…Moreover, we were able to detect close association of IP 3 R and ANO1 channels using a proximity ligation assay (PLA), a highly specific proteomics method that enables optical detection of closely associated proteins (must be within less than 40 nm proximity in order to be detected; Jarvius et al 2006;Soderberg et al 2006). In addition to the above evidence, other reports suggested that (i) GPCRs such as B 2 receptors may also co-localize with IP 3 receptors in junctional plasma membrane-ER microdomains Zhang et al 2013b) and (ii) B 2 receptors localize to plasma membrane lipid rafts in sympathetic and sensory neurons (Jeske et al 2006;Jeske, 2012;Zhang et al 2013b). In accord with these reports we found that B 2 and PAR-2 receptors co-immunoprecipitated with the IP 3 R and with the lipid raft marker caveolin-1 (Jin et al 2013).…”

Section: Simplified Schematic Diagram Illustrating Possible Relatiomentioning

confidence: 88%

“…2006; Jeske, 2012; Zhang et al . 2013 b ). In accord with these reports we found that B 2 and PAR‐2 receptors co‐immunoprecipitated with the IP 3 R and with the lipid raft marker caveolin‐1 (Jin et al .…”

Section: Coupling Between Ano1 and Endoplasmic Reticulum; Is This A Gmentioning

confidence: 98%

“…2013; Zhang et al . 2013 b ). These complexes are likely to be further supported by scaffolding proteins and cytoskeleton.…”

Section: Ano1 Containing Signalling Complexes: Future Perspectivesmentioning

confidence: 98%

“…2002; Zhang et al . 2013 b ) and (ii) B 2 receptors localize to plasma membrane lipid rafts in sympathetic and sensory neurons (Jeske et al . 2006; Jeske, 2012; Zhang et al .…”

Section: Coupling Between Ano1 and Endoplasmic Reticulum; Is This A Gmentioning

confidence: 99%

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Activation of Ca²⁺‐activated Cl⁻ channel ANO1 by localized Ca²⁺ signals

Jin

Shah

et al. 2014

The Journal of Physiology

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Ca2+‐activated chloride channels (CaCCs) regulate numerous physiological processes including epithelial transport, smooth muscle contraction and sensory processing. Anoctamin‐1 (ANO1, TMEM16A) is a principal CaCC subunit in many cell types, yet our understanding of the mechanisms of ANO1 activation and regulation are only beginning to emerge. Ca2+ sensitivity of ANO1 is rather low and at negative membrane potentials the channel requires several micromoles of intracellular Ca2+ for activation. However, global Ca2+ levels in cells rarely reach such levels and, therefore, there must be mechanisms that focus intracellular Ca2+ transients towards the ANO1 channels. Recent findings indeed indicate that ANO1 channels often co‐localize with sources of intracellular Ca2+ signals. Interestingly, it appears that in many cell types ANO1 is particularly tightly coupled to the Ca2+ release sites of the intracellular Ca2+ stores. Such preferential coupling may represent a general mechanism of ANO1 activation in native tissues.

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Section: Simplified Schematic Diagram Illustrating Possible Relatiomentioning

confidence: 88%

Section: Coupling Between Ano1 and Endoplasmic Reticulum; Is This A Gmentioning

confidence: 98%

“…2013; Zhang et al . 2013 b ). These complexes are likely to be further supported by scaffolding proteins and cytoskeleton.…”

Section: Ano1 Containing Signalling Complexes: Future Perspectivesmentioning

confidence: 98%

“…2002; Zhang et al . 2013 b ) and (ii) B 2 receptors localize to plasma membrane lipid rafts in sympathetic and sensory neurons (Jeske et al . 2006; Jeske, 2012; Zhang et al .…”

Section: Coupling Between Ano1 and Endoplasmic Reticulum; Is This A Gmentioning

confidence: 99%

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Activation of Ca²⁺‐activated Cl⁻ channel ANO1 by localized Ca²⁺ signals

Jin

Shah

et al. 2014

The Journal of Physiology

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“…Growing evidences indicate the clustering of some ion channels within lipid rafts in neurons, and thereby able to orchestrate their function. These channels include, voltage gated sodium 43 , potassium 44 and calcium channels 45 [53][54] . These clathrin-independent endocytic pathways were thought to be regulated by caveolae and by non-caveolar lipid raft carriers 55 .…”

Section: Raft Dependent Cellular Functionsmentioning

confidence: 99%

A computational approach to uncover cholesterol-rich membrane micro-domain function in health and disease

Shah¹

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Cholesterol-rich membrane microdomains, also known as lipid rafts, are specialized assemblies of membrane lipids and proteins that regulate diverse cellular events. Distinct physicochemical properties of cholesterol and sphingolipids facilitate partitioning of membrane associated proteins producing heterogeneity in the membrane bilayer. The lipid rafts are considered as signalling and sorting platforms on the cell surface that mediates clustering of signalling machinery including receptors, serine tyrosine kinases, GPI anchored and acetylated proteins. Lipid rafts are also regarded as membrane organizers that control myriads of cellular processes like endocytosis, cell adhesion and migration.Interestingly, their dysfunction has been implicated in a range of cancers, cardiovascular, and neurodegenerative diseases. Due to their apparent biological importance, various biochemical and microscopic techniques have been implemented to characterise protein constituents of cellular raft fractions along with high throughput proteomics approaches.Mass-spectrometry based proteomics profiling of lipid rafts has been pivotal in understanding the composition and spatiotemporal dynamics within these microdomains.Despite extensive proteomics research, the global protein landscape and subsequent function of lipid raft still remained elusive.In an effort to determine and understand potential lipid raft proteome profiled by multiple proteomic investigations in physiological and disease conditions this thesis describes a systematic computational approach. To achieve this, I propose and sought to fulfil three main aims (1) To develop an open source resource to characterise mammalian lipid raft proteome (2) In depth in silico characterisation of structural features and functional significance of human lipid raft associated proteins (3) To understand raft associated mechanism of tumor progression by integrative analysis of quantitative proteomics studies.In Chapter 2, I present a database for mammalian lipid raft proteome "RaftProt" (http://lipid-raft-database.di.uq.edu.au/). This online public resource is the first repository hosting a comprehensive collection lipid raft associated proteins detected through high throughput lipid raft proteomics studies. I have developed a user-friendly web platform, including number of online features, to assist searching, browsing and downloading large scale proteomics datasets. Furthermore, implementing an ontology at the backend of the RaftProt I provided a novel approach to organise and represent proteomic datasets based on anatomical features. A subset of bona-fide high confidence lipid raft proteins was proposed by applying experimental evidence based filtering criteria. Taken together, this database is a valuable resource to decipher the biological and disease specific iii organization of mammalian lipid raft proteome. Importantly, this collection effort also led the foundation for systems level characterisation of functional lipid rafts later in this project. indicate that the unifying...

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Functional responses of the hippocampus to hyperexcitability depend on directed, neuron‐specific KCNQ2 K⁺ channel plasticity

et al. 2019

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M-type (KCNQ2/3) K + channels play dominant roles in regulation of active and passive neuronal discharge properties such as resting membrane potential, spike-frequency adaptation, and hyper-excitatory states. However, plasticity of M-channel expression and function in nongenetic forms of epileptogenesis are still not well understood. Using transgenic mice with an EGFP reporter to detect expression maps of KCNQ2 mRNA, we assayed hyperexcitability-induced alterations in KCNQ2 transcription across subregions of the hippocampus. Pilocarpine and pentylenetetrazol chemoconvulsant models of seizure induction were used, and brain tissue examined 48 hr later. We observed increases in KCNQ2 mRNA in CA1 and CA3 pyramidal neurons after chemoconvulsantinduced hyperexcitability at 48 hr, but no significant change was observed in dentate gyrus (DG) granule cells. Using chromogenic in situ hybridization assays, changes to KCNQ3 transcription were not detected after hyper-excitation challenge, but the results for KCNQ2 paralleled those using the KCNQ2-mRNA reporter mice. In mice 7 days after pilocarpine challenge, levels of KCNQ2 mRNA were similar in all regions to those from control mice. In brain-slice electrophysiology recordings, CA1 pyramidal neurons demonstrated increased M-current amplitudes 48 hr after hyperexcitability; however, there were no significant changes to DG granule cell M-current amplitude. Traumatic brain injury induced significantly greater KCNQ2 expression in the hippocampal hemisphere that was ipsilateral to the trauma. In vivo, after a secondary challenge with subconvulsant dose of pentylenetetrazole, control mice were susceptible to tonicclonic seizures, whereas mice administered the M-channel opener retigabine were protected from such seizures. This study demonstrates that increased excitatory activity promotes KCNQ2 upregulation in the hippocampus in a cell-type specific manner. Such novel ion channel expressional plasticity may serve as a compensatory mechanism after a hyperexcitable event, at least in the short term. The upregulation described could be potentially leveraged in anticonvulsant enhancement of KCNQ2 channels as therapeutic target for preventing onset of epileptogenic seizures.

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Membrane microdomain determines the specificity of receptor-mediated modulation of Kv7/M potassium currents

Cited by 13 publications

References 57 publications

Activation of Ca²⁺‐activated Cl⁻ channel ANO1 by localized Ca²⁺ signals

Activation of Ca²⁺‐activated Cl⁻ channel ANO1 by localized Ca²⁺ signals

A computational approach to uncover cholesterol-rich membrane micro-domain function in health and disease

Functional responses of the hippocampus to hyperexcitability depend on directed, neuron‐specific KCNQ2 K⁺ channel plasticity

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Membrane microdomain determines the specificity of receptor-mediated modulation of Kv7/M potassium currents

Cited by 13 publications

References 57 publications

Activation of Ca2+‐activated Cl− channel ANO1 by localized Ca2+ signals

Activation of Ca2+‐activated Cl− channel ANO1 by localized Ca2+ signals

A computational approach to uncover cholesterol-rich membrane micro-domain function in health and disease

Functional responses of the hippocampus to hyperexcitability depend on directed, neuron‐specific KCNQ2 K+ channel plasticity

Contact Info

Product

Resources

About

Activation of Ca²⁺‐activated Cl⁻ channel ANO1 by localized Ca²⁺ signals

Activation of Ca²⁺‐activated Cl⁻ channel ANO1 by localized Ca²⁺ signals

Functional responses of the hippocampus to hyperexcitability depend on directed, neuron‐specific KCNQ2 K⁺ channel plasticity