Biology Commons^™

Real-Time Dynamic Imaging Of Virus Distribution In Vivo, Sean E. Hofherr, Kristen E. Adams, Christopher Y. Chen, Shannon May, Eric A. Weaver, Michael A. Barry

School of Biological Sciences: Faculty Publications

The distribution of viruses and gene therapy vectors is difficult to assess in a living organism. For instance, trafficking in murine models can usually only be assessed after sacrificing the animal for tissue sectioning or extraction. These assays are laborious requiring whole animal sectioning to ascertain tissue localization. They also obviate the ability to perform longitudinal or kinetic studies in one animal. To track viruses after systemic infection, we have labeled adenoviruses with a near-infrared (NIR) fluorophore and imaged these after intravenous injection in mice. Imaging was able to track and quantitate virus particles entering the jugular vein simultaneous with …

Characterization Of A Dipartite Iron Uptake System From Uropathogenic Escherichia Coli Strain, Doreen Koch, Anson C. K. Chan, Michael E.P. Murphy, Hauke Lilie, Gregor Grass, Dietrich H. Nies

School of Biological Sciences: Faculty Publications

In the uropathogenic Escherichia coli strain F11, in silico genome analysis revealed the dicistronic iron uptake operon fetMP, which is under iron-regulated control mediated by the Fur regulator. The expression of fetMP in a mutant strain lacking known iron uptake systems improved growth under iron depletion and increased cellular iron accumulation. FetM is a member of the iron/lead transporter superfamily and is essential for iron uptake by the Fet system. FetP is a periplasmic protein that enhanced iron uptake by FetM. Recombinant FetP bound Cu(II) and the iron analog Mn(II) at distinct sites. The crystal structure of the …

Crystallization Of Chlorella Deoxyuridine Triphosphatase, Laura Badalucco, Ishwari Poudel, Mamoru Yamanishi, Chandrasekhar Natarajan, Hideaki Moriyama

School of Biological Sciences: Faculty Publications

Deoxyuridine triphosphatase (dUTPase) is a ubiquitous enzyme that has been widely studied owing to its function and evolutionary significance. The gene coding for the dUTPase from the Chlorella alga was codon-optimized and synthesized. The synthetic gene was expressed in Escherichia coli and recombinant core Chlorella dUTPase (chdUTPase) was purified. Crystallization of chdUTPase was performed by the repetitive hanging-drop vapor-diffusion method at 298 K with ammonium sulfate as the precipitant. In the presence of 2'-deoxyuridine-5'-[(α,β)-imido]triphosphate and magnesium, the enzyme produced die-shaped hexagonal R3 crystals with unit-cell parameters a = b = 66.9, c = 93.6 A, ƴ = 120°. X-ray diffraction …

Analyses Of Fruit Flies That Do Not Express Selenoproteins Or Express The Mouse Selenoprotein, Methionine Sulfoxide Reductase B1, Reveal A Role Of Selenoproteins In Stress Resistance, Valentina A. Shchedrina, Hadise Kabil, Gerd Vorbruggen, Byung Cheon Lee, Anton A. Turanov, Mitsuko Hirosawa- Takamori, Hwa- Young Kim, Lawrence G. Harshman, Dolph L. Hatfield, Vadim N. Gladyshev

School of Biological Sciences: Faculty Publications

Selenoproteins are essential in vertebrates because of their crucial role in cellular redox homeostasis, but some invertebrates that lack selenoproteins have recently been identified. Genetic disruption of selenoprotein biosynthesis had no effect on lifespan and oxidative stress resistance of Drosophila melanogaster. In the current study, fruit flies with knock-out of the selenocysteine-specific elongation factor were metabolically labeled with ⁷⁵Se; they did not incorporate selenium into proteins and had the same lifespan on a chemically defined diet with or without selenium supplementation. These flies were, however, more susceptible to starvation than controls, and this effect could be ascribed to the …

The Arabidopsis Trithorax-Like Factor Atx1 Functions In Dehydration Stress Responses Via Aba-Dependent And Aba-Independent Pathways, Yong Ding, Zoya Avramova, Michael Fromm

School of Biological Sciences: Faculty Publications

Emerging evidence suggests that the molecular mechanisms driving the responses of plants to environmental stresses are associated with specific chromatin modifications. Here, we demonstrate that the Arabidopsis trithorax-like factor ATX1, which trimethylates histone H3 at lysine 4 (H3K4me3), is involved in dehydration stress signaling in both abscisic acid (ABA)-dependent and ABA-independent pathways. The loss of function of ATX1 results in decreased germination rates, larger stomatal apertures, more rapid transpiration and decreased tolerance to dehydration stress in atx1 plants. This deficiency is caused in part by reduced ABA biosynthesis in atx1 plants resulting from decreased transcript levels from NCED3, which …

Copper Tolerance Of Saccharomyces Cerevisiae Nonsense-Mediated Mrna Decay Mutants, Rafael Deliz-Aguirre, Audrey L. Atkin, Bessie W. Kebaara

School of Biological Sciences: Faculty Publications

The eukaryotic nonsense-mediated mRNA (NMD) is a specialized pathway that leads to the recognition and rapid degradation of mRNAs with premature termination codons, and importantly some natural mRNAs as well. Natural mRNAs with atypically long 3′-untranslated regions (UTRs) are degraded by NMD in Saccharomyces cerevisiae. A number of S. cerevisiae mRNAs undergo alternative 3′-end processing producing mRNA isoforms that differ in their 3′-UTR lengths. Some of these alternatively 3′-end processed mRNA isoforms have atypically long 3′-UTRs and would be likely targets for NMD-mediated degradation. Here, we investigated the role NMD plays in the regulation of expression of CTR2, …

Normalization And Centering Of Array-Based Heterologous Genome Hybridization Based On Divergent Control Probes, Brian J. Darby, Kenneth L. Jones, David Wheeler, Michael A. Herman

School of Biological Sciences: Faculty Publications

Background: Hybridization of heterologous (non-specific) nucleic acids onto arrays designed for model-organisms has been proposed as a viable genomic resource for estimating sequence variation and gene expression in nonmodel organisms. However, conventional methods of normalization that assume equivalent distributions (such as quantile normalization) are inappropriate when applied to non-specific (heterologous) hybridization. We propose an algorithm for normalizing and centering intensity data from heterologous hybridization that makes no prior assumptions of distribution, reduces the false appearance of homology, and provides a way for researchers to confirm whether heterologous hybridization is suitable.

Results: Data are normalized by adjusting for Gibbs free energy …

Aphids: A Model For Polyphenism And Epigenetics, Dayalan G. Srinivasan, Jennifer A. Brisson

School of Biological Sciences: Faculty Publications

Environmental conditions can alter the form, function, and behavior of organisms over short and long timescales, and even over generations. Aphid females respond to specific environmental cues by transmitting signals that have the effect of altering the development of their offspring. These epigenetic phenomena have positioned aphids as a model for the study of phenotypic plasticity. The molecular basis for this epigenetic inheritance in aphids and how this type of inheritance system could have evolved are still unanswered questions. With the availability of the pea aphid genome sequence, new genomics technologies, and ongoing genomics projects in aphids, these questions can …

Maize Cellulosic Biofuels: Soil Carbon Loss Can Be A Hidden Cost Of Residue Removal, Amy Kochsiek, Johannes Knops

School of Biological Sciences: Faculty Publications

Second generation biofuels, like cellulosic ethanol, have potential as important energy sources that can lower fossil fuel carbon emissions without affecting global food commodity prices. Agricultural crop residues, especially maize, have been proposed for use as biofuel, but the net greenhouse warming effect of the gained fossil fuel carbon offset needs to account for any ecosystem carbon losses caused by the large-scale maize residue removal. Using differential 13C isotopic ratios between residue and soil in an incubation experiment, we found that removal of residue increased soil organic matter decomposition by an average of 16%, or 540–800 kg carbon ha -1. …

Environmental And Genetic Perturbations Reveal Different Networks Of Metabolic Regulation, Anthony J. Greenberg, Sean R. Hacket, Lawrence G. Harshman, Andrew G. Clark

School of Biological Sciences: Faculty Publications

Progress in systems biology depends on accurate descriptions of biological networks. Connections in a regulatory network are identified as correlations of gene expression across a set of environmental or genetic perturbations. To use this information to predict system behavior, we must test how the nature of perturbations affects topologies of networks they reveal. To probe this question, we focused on metabolism of Drosophila melanogaster. Our source of perturbations is a set of crosses among 92 wild-derived lines from five populations, replicated in a manner permitting separate assessment of the effects of genetic variation and environmental fluctuation. We directly assayed activities …

Survival Rates Of Planidial Larvae Of The Parasitoid Fly Ormia Ochracea (Diptera: Tachinidae), Oliver M. Beckers, Cassandra M. Martin, William E. Wagner Jr.

School of Biological Sciences: Faculty Publications

The tachinid fly, Ormia ochracea Bigot 1889, is a major parasitoid of field crickets in North America. The fly ranges from Florida to California, and it has also been introduced to Hawaii. Across this range, O. ochracea uses at least 6 different Gryllus species as hosts for its larvae (Cade, 1975; Walker, 1986; Walker and Wineriter, 1991; Zuk et al., 1993; Wagner, 1996; Hedrick and Kortet, 2006). O. ochracea finds it hosts by eavesdropping on male mating songs (Cade, 1975). The fly deposits up to 3 planidial larvae (Adamo et al., 1995a) directly on the male and these …

Dtorsin, The Drosophila Ortholog Of The Early-Onset Dystonia Tor1a (Dyt1), Plays A Novel Role In Dopamine Metabolism, Noriko Wakabayashi-Ito, Olugbenga M. Doherty, Hideaki Moriyama, Xandra O. Breakefield, James F. Gusella, Janis M. O’Donnell, Naoto Ito

School of Biological Sciences: Faculty Publications

Dystonia represents the third most common movement disorder in humans. At least 15 genetic loci (DYT1-15) have been identified and some of these genes have been cloned. TOR1A (formally DYT1), the gene responsible for the most common primary hereditary dystonia, encodes torsinA, an AAA ATPase family protein. However, the function of torsinA has yet to be fully understood. Here, we have generated and characterized a complete loss-of-function mutant for dtorsin, the only Drosophila ortholog of TOR1A. Null mutation of the X-linked dtorsin was semi-lethal with most male flies dying by the prepupal stage and the few surviving …

Vapc6, A Ribonucleolytic Toxin Regulates Thermophilicity In The Crenarchaeote Sulfolobus Solfataricus, Yukari Maezato, Amanda Daugherty, Karl Dana, Edith Soo, Charlotte Cooper, Sabrina Tachdjian, Robert M. Kelly, Paul H. Blum

School of Biological Sciences: Faculty Publications

The phylum Crenarchaeota includes hyperthermophilic micro-organisms subjected to dynamic thermal conditions. Previous transcriptomic studies of Sulfolobus solfataricus identified vapBC6 as a heat-shock (HS)-inducible member of the Vap toxin– antitoxin gene family. In this study, the inactivation of the vapBC6 operon by targeted gene disruption produced two recessive phenotypes related to fitness, HS sensitivity and a heat-dependent reduction in the rate of growth. In-frame vapBC6 deletion mutants were analyzed to examine the respective roles of each protein. Since vapB6 transcript abundance was elevated in the vapC6 deletion, the VapC6 toxin appears to regulate abundance of its cognate antitoxin. In contrast, vapC6 …

Composite Effects Of Polymorphisms Near Multiple Regulatory Elements Create A Major-Effect Qtl, Ryan D. Bickel, Artyom Kopp, Sergey V. Nuzhdin

School of Biological Sciences: Faculty Publications

Many agriculturally, evolutionarily, and medically important characters vary in a quantitative fashion. Unfortunately, the genes and sequence variants accounting for this variation remain largely unknown due to a variety of biological and technical challenges. Drosophila melanogaster contains high levels of sequence variation and low linkage disequilibrium, allowing us to dissect the effects of many causative variants within a single locus. Here, we take advantage of these features to identify and characterize the sequence polymorphisms that comprise major effect QTL alleles segregating at the bric-a-brac locus. We show that natural bric-a-brac alleles with large effects on cuticular pigmentation reflect a cumulative …

Epigenetic Regulatory Mechanisms In Plants, Zoya Avramova

School of Biological Sciences: Faculty Publications

Genomes are defined by their primary sequence, which provides the genetic blueprint of a species. Eukaryotic DNA functions within the context of chromatin, which provides additional layers of gene regulation referred to as “epigenetic.” The commonly found definition of epigenetics is that of a “study of heritable changes in genome function that occur without a change in DNA sequence.” However, evidence that neuronal gene-expression states are also regulated by epigenetic mechanisms, despite evidence that neuronal cells do not divide, has opened space for a broader unifying definition that keeps “the sense of prevailing usage but avoids constraints imposed by stringently …

Sex Chromosome-Specific Regulation In The Drosophila Male Germline But Little Evidence For Chromosomal Dosage Compensation Or Meiotic Inactivation, Colin D. Meiklejohn, Emily L. Landeen, Jodi M. Cook, Sarah B. Kingan, Daven C. Presgraves

School of Biological Sciences: Faculty Publications

The evolution of heteromorphic sex chromosomes (e.g., XY in males or ZW in females) has repeatedly elicited the evolution of two kinds of chromosome-specific regulation: dosage compensation—the equalization of X chromosome gene expression in males and females— and meiotic sex chromosome inactivation (MSCI)—the transcriptional silencing and heterochromatinization of the X during meiosis in the male (or Z in the female) germline. How the X chromosome is regulated in the Drosophila melanogaster male germline is unclear. Here we report three new findings concerning gene expression from the X in Drosophila testes. First, X chromosome-wide dosage compensation appears to be absent from …

Arabidopsis G-Protein Interactome Reveals Connections To Cell Wall Carbohydrates And Morphogenesis, Karsten Klopffleisch, Nguyen Phan, Kelsey Augustin, Robert S. Bayne, Katherine S. Booker, Jose R. Botella, Nicholas C. Carpita, Tyrell Carr, Jin-Gui Chen, Thomas Ryan Cooke, Arwen Frick-Cheng, Erin J. Friedman, Brandon Fulk, Michael G. Hahn, Kun Jiang, Lucia Jorda, Lydia Kruppe, Chenggang Liu, Justine Lorek, Maureen C. Mccann, Antonio Molina, Etsuko N. Moriyama, M. Shahid Mukhtar, Yashwanti Mudgil, Sivakumar Pattathil, John Schwarz, Steven Seta, Matthew Tan, Ulrike Temp, Yuri Trusov, Daisuke Urano, Bastian Welter, Jing Yang, Ralph Panstruga, Joachim F. Uhrig, Alan M. Jones

School of Biological Sciences: Faculty Publications

The heterotrimeric G-protein complex is minimally composed of Ga, Gb, and Gc subunits. In the classic scenario, the G-protein complex is the nexus in signaling from the plasma membrane, where the heterotrimeric G-protein associates with heptahelical G-protein-coupled receptors (GPCRs), to cytoplasmic target proteins called effectors. Although a number of effectors are known in metazoans and fungi, none of these are predicted to exist in their canonical forms in plants. To identify ab initio plant G-protein effectors and scaffold proteins, we screened a set of proteins from the G-protein complex using two-hybrid complementation in yeast. After deep and exhaustive interrogation, we …

Interferon Regulatory Factor 4 (Irf-4) Targets Irf-5 To Regulate Epstein-Barr Virus Transformation, Dongsheng Xu, Florencia Meyer, Erica Ehlers, Laura Blasnitz, Luwen Zhang

School of Biological Sciences: Faculty Publications

The cellular interferon regulatory factor-4 (IRF-4), which is a member of IRF family, is involved in the development of multiple myeloma and Epstein-Barr virus (EBV)-mediated transformation of B lymphocytes. However, the molecular mechanism of IRF-4 in cellular transformation is unknown. We have found that knockdown of IRF-4 leads to high expression of IRF-5, a pro-apoptotic member in the IRF family. Overexpression of IRF-4 represses IRF-5 expression. Reduction of IRF-4 leads to growth inhibition, and the restoration of IRF-4 by exogenous plasmids correlates with the growth recovery and reduces IRF-5 expression. In addition, IRF-4 negatively regulates IRF-5 promoter reporter activities and …

A Detailed Phylogenetic Analysis Of Fiv In The United States, Eric A. Weaver

School of Biological Sciences: Faculty Publications

Background: Feline immunodeficiency virus (FIV) is a lentivirus associated with AIDS-like illnesses in cats and has been used as a model for the study of human immunodeficiency virus (HIV). A feature of HIV and FIV infection is the continually increasing divergence among viral isolates between different individuals, as well as within the same individuals.

Methodology/Principal Findings: The goal of this study was to determine the phylogenetic patterns of viral isolates obtained within the United States (U.S.) by focusing on the variable, V3-V4, region of the FIV envelope gene.

Conclusions/Significance: Data indicate that FIV, from within the U.S., localize to four …

The Spatial Influence Of Aboveground Diversity On Belowground Communities, T. Bliss, Tom Powers, Chad Brassil

School of Biological Sciences: Faculty Publications

Little is known about the effect of diversity surrounding a focal plant species on the belowground community under that species. At least two alternative hypotheses exist. First, studies involving a range of ecosystems and taxonomic groups have shown that changes in diversity in one group of species can promote diversity in other groups. Alternatively, many studies in soil ecology have shown that belowground communities are strongly determined by the dominant aboveground species. To better understand the role of aboveground diversity on belowground communities, we examined soil nematode communities directly under Panicum virgatum (switchgrass) in areas of high and low surrounding …

Positive Carotenoid Balance Correlates With Greater Reproductive Performance In A Wild Bird, Rebecca Safran, Kevin J. Mcgraw, Matt Wilkins, Joanna K. Hubbard, Julie Marling

School of Biological Sciences: Faculty Publications

Background: Carotenoids can confer somatic and reproductive benefits, but most evidence is from captive animal experimentation or single time-point sampling. Another perhaps more informative means by which to assess physiological contributions to animal performance is by tracking an individual’s ability to increase or sustain carotenoids or other health-related molecules over time, as these are likely to be temporally variable.

Methodology/Principal Findings: In a field study of North American barn swallows (Hirundo rustica erythrogaster), we analyzed within-individual changes in carotenoid concentrations by repeatedly sampling the carotenoid profiles of individuals over the course of the breeding season. Our results demonstrate …

The Role Of Litter Quality Feedbacks In Terrestrial Nitrogen And Phosphorus Cycling, Johannes M.H. Knops, David A. Wedin, Shahid Naeem

School of Biological Sciences: Faculty Publications

Many studies in ecosystem ecology argue for strong control of litter quality over nitrogen (N) cycling. We developed a model for temperate grasslands to test the importance of litter quality in decomposition for N and phosphorus (P) cycling based on the following premises. First, terrestrial N and P cycling differ fundamentally because N is a structural component of the soil organic matter (SOM), whereas P is not. Secondly, SOM has a much lower C:N ratio than litter inputs. Thirdly, litter decomposition follows an exponential decay with 20% of the original litter mass turning into SOM. Fourth, litter N concentration shows …

Genetic Conflict And Sex Chromosome Evolution, Colin D. Meiklejohn, Yun Tao

School of Biological Sciences: Faculty Publications

Chromosomal sex determination systems create the opportunity for the evolution of selfish genetic elements that increase the transmission of one sex chromosome at the expense of its homolog. Because such selfish elements on sex chromosomes can reduce fertility and distort the sex ratio of progeny, unlinked suppressors are expected to evolve, bringing different regions of the genome into conflict over the meiotic transmission of the sex chromosomes. Here we argue that recurrent genetic conflict over sex chromosome transmission is an important evolutionary force that has shaped a wide range of seemingly disparate phenomena including the epigenetic regulation of genes expressed …

Integrating Spatial And Temporal Approaches To Understanding Species Richness, Ethan P. White, S. K. Morgan Ernest, Peter B. Adler, Allen H. Hurlbert, S. Kathleen Lyons

School of Biological Sciences: Faculty Publications

Understanding species richness patterns represents one of the most fundamental problems in ecology. Most research in this area has focused on spatial gradients of species richness, with a smaller area of emphasis dedicated to understanding the temporal dynamics of richness. However, few attempts have been made to understand the linkages between the spatial and temporal patterns related to richness. Here, we argue that spatial and temporal richness patterns and the processes that drive them are inherently linked, and that our understanding of richness will be substantially improved by considering them simultaneously. The species–time–area relationship provides a case in point: successful …

Analysis Of Mirna Modifications, Bin Yu, Xuemei Chen

School of Biological Sciences: Faculty Publications

After transcription, a large number of cellular RNAs employ modifications to increase their diversity and functional potential. Modifications can occur on the base, ribose, or both, and are important steps in the maturation of many RNAs. Our lab recently showed that plant microRNAs (miRNAs) possess a 2′-O-methyl group on the ribose of the 3′ terminal nucleotide, and that this methyl group is added after miRNA/miRNA* formation. One function of this modification is to protect miRNAs from 3′ terminal uridylation by an unknown enzymatic activity. It is possible that uridylation of miRNAs triggers their degradation. Here we describe a …

Nm23-H1 Can Induce Cell Cycle Arrest And Apoptosis In B Cells, Tathagata Choudhuri, Masanao Murakami, Rajeev Kaul, Sushil K. Sahu, Suchitra Mohanty, Subhash C. Verma, Pankaj Kumar, Erle S. Robertson

School of Biological Sciences: Faculty Publications

Nm23-H1 is a well-known tumor metastasis suppressor, which functions as a nucleoside-diphosphate kinase converting nucleoside diphosphates to nucleoside triphosphates with an expense of ATP. It regulates a variety of cellular activities, including proliferation, development, migration and differentiation known to be modulated by a series of complex signaling pathway. Few studies have addressed the mechanistic action of Nm23-H1 in the context of these cellular processes. To determine the downstream pathways modulated by Nm23-H1, we expressed Nm23-H1 in a Burkitt lymphoma derived B-cell line BJAB and performed pathway specific microarray analysis. The genes with significant changes in expression patterns were clustered in …

Increased Dendrite Branching In Aβpp/Ps1 Mice And Elongation Of Dendrite Arbors By Fasudil Administration, Brian A. Couch, George J. Demarco, Shannon L. Gourley, Anthony J. Koleske

School of Biological Sciences: Faculty Publications

Amyloid-β (Aβ) overproduction and dendrite arbor atrophy are hallmarks of Alzheimer’s disease. The RhoA GTPase (Rho) signals through Rho kinase (ROCK) to control cytoskeletal dynamics and regulate neuron structure. Hyperactive Rho signaling destabilizes neurons leading to dendritic regression that can be rescued by genetic or pharmacological reduction of ROCK signaling. To understand what effect reduced ROCK signaling has on the dendrite arbors of mice that overproduce Aβ, we administered the ROCK inhibitor fasudil to AβPP/PS1 transgenic mice. We report that increased dendrite branching occurs in AβPP/PS1 mice and that fasudil promotes …

The Abl And Arg Non-Receptor Tyrosine Kinases Regulate Different Zones Of Stress Fiber, Focal Adhesion, And Contractile Network Localization In Spreading Fibroblasts, Justin G. Peacock, Brian A. Couch, Anthony J. Koleske

School of Biological Sciences: Faculty Publications

Directed cell migration requires precise spatial control of F-actin-based leading edge protrusion, focal adhesion (FA) dynamics, and actomyosin contractility. In spreading fibroblasts, the Abl family kinases, Abl and Arg, primarily localize to the nucleus and cell periphery, respectively. Here we provide evidence that Abl and Arg exert different spatial regulation on cellular contractile and adhesive structures. Loss of Abl function reduces FA, F-actin, and phosphorylated myosin light chain (pMLC) staining at the cell periphery, shifting the distribution of these elements more to the center of the cell than in wild-type (WT) and arg^—/— cells. Conversely, loss of Arg function …

Mitochondrial-Nuclear Epistasis Affects Fitness Within Species But Does Not Contribute To Fixed Incompatibilities Between Species Of Drosophila, Kristi L. Montooth, Colin D. Meiklejohn, Dawn N. Abt, David M. Rand

School of Biological Sciences: Faculty Publications

Efficient mitochondrial function requires physical interactions between the proteins encoded by the mitochondrial and nuclear genomes. Co-evolution between these genomes may result in the accumulation of incompatibilities between divergent lineages. We test whether mitochondrialnuclear incompatibilities have accumulated within the Drosophila melanogaster species subgroup by combining divergent mitochondrial and nuclear lineages and quantifying the effects on relative fitness. Precise placement of nine mtDNAs from D. melanogaster, D. simulans and D. mauritiana into two D. melanogaster nuclear genetic backgrounds reveals significant mitochondrial-nuclear epistasis affecting fitness in females. Combining the mitochondrial genomes with three different D. melanogaster X chromosomes reveals significant epistasis …

Synaptic Clustering Of Psd-95 Is Regulated By C-Abl Through Tyrosine Phosphorylation, Karen Perez De Arce, Lorena Varela-Nallar, Olivia Farias, Alejandra Cifuentes, Paulina Bull, Brian A. Couch, Anthony J. Koleske, Nibaldo C. Inestrosa, Alejandra R. Alvarez

School of Biological Sciences: Faculty Publications

The c-Abl tyrosine kinase is present in mouse brain synapses, but its precise synaptic function is unknown. We found that c-Abl levels in the rat hippocampus increase postnatally, with expression peaking at the first postnatal week. In 14 d in vitro hippocampal neuron cultures, c-Abl localizes primarily to the postsynaptic compartment, in which it colocalizes with the postsynaptic scaffold protein postsynaptic density protein-95 (PSD-95) in apposition to presynaptic markers. c-Abl associates with PSD-95, and chemical or genetic inhibition of c-Abl kinase activity reduces PSD-95 tyrosine phosphorylation, leading to reduced PSD-95 clustering and reduced synapses in treated neurons. c-Abl can phosphorylate …