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Diane lipscombe

Diane Lipscombe, Eduardo Javier Lopez-Soto
Cell-specific regulation of gene expression is important for maintaining cortical excitatory/inhibitory balance. In this issue of Neuron, Vuong et al. (2018) reveal an unlikely role for a broadly expressed RNA binding protein, Rbfox1, in protecting inhibitory transmission in the hippocampus.
April 4, 2018: Neuron
Summer E Allen, Cecilia P Toro, Arturo Andrade, Eduardo J López-Soto, Sylvia Denome, Diane Lipscombe
The majority of multiexon mammalian genes contain alternatively spliced exons that have unique expression patterns in different cell populations and that have important cell functions. The expression profiles of alternative exons are controlled by cell-specific splicing factors that can promote exon inclusion or exon skipping but with few exceptions we do not know which specific splicing factors control the expression of alternatively spliced exons of known biological function. Many ion channel genes undergo extensive alternative splicing including Cacna1b that encodes the voltage-gated CaV 2...
September 2017: ENeuro
Emilio R Mustafá, Eduardo J López Soto, Valentina Martínez Damonte, Silvia S Rodríguez, Diane Lipscombe, Jesica Raingo
Voltage-gated Ca2+ (CaV ) channels couple membrane depolarization to Ca2+ influx, triggering a range of Ca2+ -dependent cellular processes. CaV channels are, therefore, crucial in shaping neuronal activity and function, depending on their individual temporal and spatial properties. Furthermore, many neurotransmitters and drugs that act through G protein coupled receptors (GPCRs), modulate neuronal activity by altering the expression, trafficking, or function of CaV channels. GPCR-dependent mechanisms that downregulate CaV channel expression levels are observed in many neurons but are, by comparison, less studied...
November 15, 2017: Journal of Cell Science
Xia-Jing Tong, Eduardo Javier López-Soto, Lei Li, Haowen Liu, Daniel Nedelcu, Diane Lipscombe, Zhitao Hu, Joshua M Kaplan
The synaptic adhesion molecules Neurexin and Neuroligin alter the development and function of synapses and are linked to autism in humans. In C. elegans, post-synaptic Neurexin (NRX-1) and pre-synaptic Neuroligin (NLG-1) mediate a retrograde synaptic signal that inhibits acetylcholine (ACh) release at neuromuscular junctions. Here, we show that the retrograde signal decreases ACh release by inhibiting the function of pre-synaptic UNC-2/CaV2 calcium channels. Post-synaptic NRX-1 binds to an auxiliary subunit of pre-synaptic UNC-2/CaV2 channels (UNC-36/α2δ), decreasing UNC-36 abundance at pre-synaptic elements...
July 19, 2017: Neuron
Patrick J O'Hern, Inês do Carmo G Gonçalves, Johanna Brecht, Eduardo Javier López Soto, Jonah Simon, Natalie Chapkis, Diane Lipscombe, Min Jeong Kye, Anne C Hart
Spinal Muscular Atrophy (SMA) is caused by diminished Survival of Motor Neuron (SMN) protein, leading to neuromuscular junction (NMJ) dysfunction and spinal motor neuron (MN) loss. Here, we report that reduced SMN function impacts the action of a pertinent microRNA and its mRNA target in MNs. Loss of the C. elegans SMN ortholog, SMN-1, causes NMJ defects. We found that increased levels of the C. elegans Gemin3 ortholog, MEL-46, ameliorates these defects. Increased MEL-46 levels also restored perturbed microRNA (miR-2) function in smn-1(lf) animals...
May 2, 2017: ELife
Diane Lipscombe, Jen Q Pan, Stephanie Schorge
What is the topic of this review? We discuss tools available to access genome-wide data sets that harbour cell-specific, brain region-specific and tissue-specific information on exon usage for several species, including humans. In this Review, we demonstrate how to access this information in genome databases and its enormous value to physiology. What advances does it highlight? The sheer scale of protein diversity that is possible from complex genes, including those that encode voltage-gated ion channels, is vast...
December 2015: Experimental Physiology
Diane Lipscombe, Arturo Andrade
Voltage-gated calcium ion channels are essential for numerous biological functions of excitable cells and there is wide spread appreciation of their importance as drug targets in the treatment of many disorders including those of cardiovascular and nervous systems. Each Cacna1 gene has the potential to generate a number of structurally, functionally, and in some cases pharmacologically unique CaVα1 subunits through alternative pre-mRNA splicing and the use of alternate promoters. Analyses of rapidly emerging deep sequencing data for a range of human tissue transcriptomes contain information to quantify tissue-specific and alternative exon usage patterns for Cacna1 genes...
2015: Current Molecular Pharmacology
Justus L Groen, Arturo Andrade, Katja Ritz, Hamid Jalalzadeh, Martin Haagmans, Ted E J Bradley, Aldo Jongejan, Dineke S Verbeek, Peter Nürnberg, Sylvia Denome, Raoul C M Hennekam, Diane Lipscombe, Frank Baas, Marina A J Tijssen
Using exome sequencing and linkage analysis in a three-generation family with a unique dominant myoclonus-dystonia-like syndrome with cardiac arrhythmias, we identified a mutation in the CACNA1B gene, coding for neuronal voltage-gated calcium channels CaV2.2. This mutation (c.4166G>A;p.Arg1389His) is a disruptive missense mutation in the outer region of the ion pore. The functional consequences of the identified mutation were studied using whole-cell and single-channel patch recordings. High-resolution analyses at the single-channel level showed that, when open, R1389H CaV2...
February 15, 2015: Human Molecular Genetics
Yu-Qiu Jiang, Arturo Andrade, Diane Lipscombe
Presynaptic voltage-gated calcium Ca(V)2.2 channels play a privileged role in spinal level sensitization following peripheral nerve injury. Direct and indirect inhibitors of Ca(V)2.2 channel activity in spinal dorsal horn are analgesic in chronic pain states. Ca(V)2.2 channels represent a family of splice isoforms that are expressed in different combinations according to cell-type. A pair of mutually exclusive exons in the Ca(V)2.2 encoding Cacna1b gene, e37a and e37b, differentially influence morphine analgesia...
December 26, 2013: Molecular Pain
Diane Lipscombe, Summer E Allen, Cecilia P Toro
Voltage-gated calcium ion (CaV) channels convert neuronal activity into rapid intracellular calcium signals to trigger a myriad of cellular responses. Their involvement in major neurological and psychiatric diseases, and importance as therapeutic targets, has propelled interest in subcellular-specific mechanisms that align CaV channel activity to specific tasks. Here, we highlight recent studies that delineate mechanisms controlling the expression of CaV channels at the level of RNA and protein. We discuss the roles of RNA editing and alternative pre-mRNA splicing in generating CaV channel isoforms with activities specific to the demands of individual cells; the roles of ubiquitination and accessory proteins in regulating CaV channel expression; and the specific binding partners that contribute to both pre- and postsynaptic CaV channel function...
October 2013: Trends in Neurosciences
Ann S Hamilton, Xiao-Cheng Wu, Joseph Lipscomb, Steven T Fleming, Mary Lo, Dian Wang, Michael Goodman, Alex Ho, Jean B Owen, Chandrika Rao, Robert R German
Data on initial treatment of 8232 cases of localized prostate cancer diagnosed in 2004 were obtained by medical record abstraction (including hospital and outpatient locations) from seven state cancer registries participating in the Centers for Disease Control and Prevention's Breast and Prostate Cancer Data Quality and Patterns of Care Study. Distinction was made between men receiving no therapy with no monitoring plan (no therapy/no plan [NT/NP]) and those receiving active surveillance (AS). Overall, 8.6% received NT/NP and 4...
December 2012: Journal of the National Cancer Institute. Monographs
Diane Lipscombe, Arturo Andrade, Summer E Allen
Neuronal voltage-gated calcium channels generate rapid, transient intracellular calcium signals in response to membrane depolarization. Neuronal Ca(V) channels regulate a range of cellular functions and are implicated in a variety of neurological and psychiatric diseases including epilepsy, Parkinson's disease, chronic pain, schizophrenia, and bipolar disorder. Each mammalian Cacna1 gene has the potential to generate tens to thousands of Ca(V) channels by alternative pre-mRNA splicing, a process that adds fine granulation to the pool of Ca(V) channel structures and functions...
July 2013: Biochimica et Biophysica Acta
Spiro Marangoudakis, Arturo Andrade, Thomas D Helton, Sylvia Denome, Andrew J Castiglioni, Diane Lipscombe
Ca(V)2.2 (N-type) calcium channels control the entry of calcium into neurons to regulate essential functions but most notably presynaptic transmitter release. Ca(V)2.2 channel expression levels are precisely controlled, but we know little of the cellular mechanisms involved. The ubiquitin proteasome system (UPS) is known to regulate expression of many synaptic proteins, including presynaptic elements, to optimize synaptic efficiency. However, we have limited information about ubiquitination of Ca(V)2 channels...
July 25, 2012: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Summer E Allen, Robert B Darnell, Diane Lipscombe
Many cellular processes are involved in optimizing protein function for specific neuronal tasks; here we focus on alternative pre-mRNA splicing. Alternative pre-mRNA splicing gives cells the capacity to modify and selectively re-balance their existing pool of transcripts in a coordinated way across multiple mRNAs, thereby effecting relatively rapid and relatively stable changes in protein activity. Here we report on and discuss the coordinated regulation of two sites of alternative splicing, e24a and e31a, in P-type CaV2...
November 2010: Channels
Arturo Andrade, Sylvia Denome, Yu-Qiu Jiang, Spiro Marangoudakis, Diane Lipscombe
Alternative pre-mRNA splicing occurs extensively in the nervous systems of complex organisms, including humans, considerably expanding the potential size of the proteome. Cell-specific alternative pre-mRNA splicing is thought to optimize protein function for specialized cellular tasks, but direct evidence for this is limited. Transmission of noxious thermal stimuli relies on the activity of N-type Ca(V)2.2 calcium channels in nociceptors. Using an exon-replacement strategy in mice, we show that mutually exclusive splicing patterns in the Ca(V)2...
October 2010: Nature Neuroscience
Arturo Andrade, Alejandro Sandoval, Ricardo González-Ramírez, Diane Lipscombe, Kevin P Campbell, Ricardo Felix
The auxiliary Ca(V)alpha(2)delta-1 subunit is an important component of voltage-gated Ca(2+) (Ca(V)) channel complexes in many tissues and of great interest as a drug target. Nevertheless, its exact role in specific cell functions is still unknown. This is particularly important in the case of the neuronal L-type Ca(V) channels where these proteins play a key role in the secretion of neurotransmitters and hormones, gene expression, and the activation of other ion channels. Therefore, using a combined approach of patch-clamp recordings and molecular biology, we studied the role of the Ca(V)alpha(2)delta-1 subunit on the functional expression and the pharmacology of recombinant L-type Ca(V)1...
October 2009: Cell Calcium
Lorin M Jakubek, Spiro Marangoudakis, Jesica Raingo, Xinyuan Liu, Diane Lipscombe, Robert H Hurt
Carbon nanotubes (CNTs) are used with increasing frequency in neuroengineering applications. CNT scaffolds are used to transmit electrical stimulation to cultured neurons and to control outgrowth and branching patterns of neurites. CNTs have been reported to disrupt normal neuronal function including alterations in endocytotic capability and inhibition of ion channels. Calcium ion channels regulate numerous neuronal and cellular functions including endo and exocytosis, neurite outgrowth, and gene expression...
October 2009: Biomaterials
Diane Lipscombe, Jennifer Qian Pan
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate neuronal excitability, pacemaking, dendritic integration, and homeostatic plasticity and are culprits in aberrant neuronal activity in certain epilepsies. In this issue of Neuron two manuscripts (Santoro et al. and Zolles et al.) report that HCN channel gating and expression are controlled by Trip8b (Pex5R) but with a bidirectional spin.
June 25, 2009: Neuron
Michael Goodman, Lyn Almon, Rana Bayakly, Susan Butler, Carol Crosby, Colleen DiIorio, Donatus Ekwueme, Diane Fletcher, John Fowler, Theresa Gillespie, Karen Glanz, Ingrid Hall, Judith Lee, Jonathan Liff, Joseph Lipscomb, Lori A Pollack, Lisa C Richardson, Phillip Roberts, Kyle Steenland, Kevin Ward
Whereas, most cancer research data come from high-profile academic centers, little is known about the outcomes of cancer care in rural communities. We summarize the experience of building a multi-institution partnership to develop a cancer outcomes research infrastructure in Southwest Georgia (SWGA), a primarily rural 33-county area with over 700,000 residents. The partnership includes eight institutions: the Emory University in Atlanta, the Centers for Disease Control and Prevention (CDC), the Georgia Comprehensive Center Registry (the Registry), the Southwest Georgia Cancer Coalition (the Coalition), and the four community cancer centers located within the SWGA region...
February 2009: Journal of Community Health
Diane Lipscombe, Jesica Raingo
How many different calcium channels does it take to make a nervous system? The answer: more than any of us predicted. In 1975 Hagiwara and colleagues published the first evidence that functionally different calcium channels are expressed in cells. By 1999, the calcium channel family could boast ten members, each member defined by a unique set of attributes to support their cellular functions and by unique amino acid sequences. Although nine of these genes are expressed in the nervous system, that number still seemed insufficient to support the wide spectrum of neuronal functions controlled by voltage-gated calcium channels...
July 2007: Channels
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