Visualizing K48 Ubiquitination during Presynaptic Formation By Ubiquitination-Induced Fluorescence Complementation (UiFC).

Abstract:

:In recent years, signaling through ubiquitin has been shown to be of great importance for normal brain development. Indeed, fluctuations in ubiquitin levels and spontaneous mutations in (de)ubiquitination enzymes greatly perturb synapse formation and neuronal transmission. In the brain, expression of lysine (K) 48-linked ubiquitin chains is higher at a developmental stage coincident with synaptogenesis. Nevertheless, no studies have so far delved into the involvement of this type of polyubiquitin chains in synapse formation. We have recently proposed a role for polyubiquitinated conjugates as triggering signals for presynaptic assembly. Herein, we aimed at characterizing the axonal distribution of K48 polyubiquitin and its dynamics throughout the course of presynaptic formation. To accomplish so, we used an ubiquitination-induced fluorescence complementation (UiFC) strategy for the visualization of K48 polyubiquitin in live hippocampal neurons. We first validated its use in neurons by analyzing changing levels of polyubiquitin. UiFC signal is diffusely distributed with distinct aggregates in somas, dendrites and axons, which perfectly colocalize with staining for a K48-specific antibody. Axonal UiFC aggregates are relatively stable and new aggregates are formed as an axon grows. Approximately 65% of UiFC aggregates colocalize with synaptic vesicle clusters and they preferentially appear in the axonal domains of axo-somatodendritic synapses when compared to isolated axons. We then evaluated axonal accumulation of K48 ubiquitinated signals in bead-induced synapses. We observed rapid accumulation of UiFC signal and endogenous K48 ubiquitin at the sites of newly formed presynapses. Lastly, we show by means of a microfluidic platform, for the isolation of axons, that presynaptic clustering on beads is dependent on E1-mediated ubiquitination at the axonal level. Altogether, these results indicate that enrichment of K48 polyubiquitin at the site of nascent presynaptic terminals is an important axon-intrinsic event for presynaptic differentiation.

journal_name

Front Mol Neurosci

authors

Pinto MJ,Pedro JR,Costa RO,Almeida RD

doi

10.3389/fnmol.2016.00043

subject

Has Abstract

pub_date

2016-06-10 00:00:00

pages

43

issn

1662-5099

journal_volume

9

pub_type

杂志文章
  • N-Glycosylation Regulates the Trafficking and Surface Mobility of GluN3A-Containing NMDA Receptors.

    abstract::N-methyl-D-aspartate receptors (NMDARs) play critical roles in both excitatory neurotransmission and synaptic plasticity. NMDARs containing the nonconventional GluN3A subunit have different functional properties compared to receptors comprised of GluN1/GluN2 subunits. Previous studies showed that GluN1/GluN2 receptors...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2018.00188

    authors: Skrenkova K,Lee S,Lichnerova K,Kaniakova M,Hansikova H,Zapotocky M,Suh YH,Horak M

    更新日期:2018-06-04 00:00:00

  • PAK6 Phosphorylates 14-3-3γ to Regulate Steady State Phosphorylation of LRRK2.

    abstract::Mutations in Leucine-rich repeat kinase 2 (LRRK2) are associated with Parkinson's disease (PD) and, as such, LRRK2 is considered a promising therapeutic target for age-related neurodegeneration. Although the cellular functions of LRRK2 in health and disease are incompletely understood, robust evidence indicates that P...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2017.00417

    authors: Civiero L,Cogo S,Kiekens A,Morganti C,Tessari I,Lobbestael E,Baekelandt V,Taymans JM,Chartier-Harlin MC,Franchin C,Arrigoni G,Lewis PA,Piccoli G,Bubacco L,Cookson MR,Pinton P,Greggio E

    更新日期:2017-12-14 00:00:00

  • Molecular Mechanisms of Lithium Action: Switching the Light on Multiple Targets for Dementia Using Animal Models.

    abstract::Lithium has long been used for the treatment of psychiatric disorders, due to its robust beneficial effect as a mood stabilizing drug. Lithium's effectiveness for improving neurological function is therefore well-described, stimulating the investigation of its potential use in several neurodegenerative conditions incl...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2018.00297

    authors: Kerr F,Bjedov I,Sofola-Adesakin O

    更新日期:2018-08-28 00:00:00

  • Metabotropic Glutamate Receptor 7: A New Therapeutic Target in Neurodevelopmental Disorders.

    abstract::Neurodevelopmental disorders (NDDs) are characterized by a wide range of symptoms including delayed speech, intellectual disability, motor dysfunction, social deficits, breathing problems, structural abnormalities, and epilepsy. Unfortunately, current treatment strategies are limited and innovative new approaches are ...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fnmol.2018.00387

    authors: Fisher NM,Seto M,Lindsley CW,Niswender CM

    更新日期:2018-10-23 00:00:00

  • Corrigendum: β2-Adrenergic Receptor-Mediated HIF-1α Upregulation Mediates Blood Brain Barrier Damage in Acute Cerebral Ischemia.

    abstract::[This corrects the article on p. 257 in vol. 10, PMID: 28855859.]. ...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章,已发布勘误

    doi:10.3389/fnmol.2017.00392

    authors: Sun Y,Chen X,Zhang X,Shen X,Wang M,Wang X,Liu WC,Liu CF,Liu J,Liu W,Jin X

    更新日期:2017-11-20 00:00:00

  • LRP1 Modulates APP Intraneuronal Transport and Processing in Its Monomeric and Dimeric State.

    abstract::The low-density lipoprotein receptor-related protein 1, LRP1, interacts with APP and affects its processing. This is assumed to be mostly caused by the impact of LRP1 on APP endocytosis. More recently, also an interaction of APP and LRP1 early in the secretory pathway was reported whereat retention of LRP1 in the ER l...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2017.00118

    authors: Herr UM,Strecker P,Storck SE,Thomas C,Rabiej V,Junker A,Schilling S,Schmidt N,Dowds CM,Eggert S,Pietrzik CU,Kins S

    更新日期:2017-04-27 00:00:00

  • Target Molecules of STIM Proteins in the Central Nervous System.

    abstract::Stromal interaction molecules (STIMs), including STIM1 and STIM2, are single-pass transmembrane proteins that are located predominantly in the endoplasmic reticulum (ER). They serve as calcium ion (Ca2+) sensors within the ER. In the central nervous system (CNS), they are involved mainly in Orai-mediated store-operate...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fnmol.2020.617422

    authors: Serwach K,Gruszczynska-Biegala J

    更新日期:2020-12-23 00:00:00

  • Regulation of AMPA Receptor Trafficking by Protein Ubiquitination.

    abstract::The molecular mechanisms underlying plastic changes in the strength and connectivity of excitatory synapses have been studied extensively for the past few decades and remain the most attractive cellular models of learning and memory. One of the major mechanisms that regulate synaptic plasticity is the dynamic adjustme...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fnmol.2017.00347

    authors: Widagdo J,Guntupalli S,Jang SE,Anggono V

    更新日期:2017-10-26 00:00:00

  • Stress and addiction: contribution of the corticotropin releasing factor (CRF) system in neuroplasticity.

    abstract::Corticotropin releasing factor (CRF) has been shown to induce various behavioral changes related to adaptation to stress. Dysregulation of the CRF system at any point can lead to a variety of psychiatric disorders, including substance use disorders (SUDs). CRF has been associated with stress-induced drug reinforcement...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2012.00091

    authors: Haass-Koffler CL,Bartlett SE

    更新日期:2012-09-06 00:00:00

  • Immune Checkpoint Blockade - How Does It Work in Brain Metastases?

    abstract::Immune checkpoints restrain the immune system following its activation and their inhibition unleashes anti-tumor immune responses. Immune checkpoint inhibitors revolutionized the treatment of several cancer types, including melanoma, and immune checkpoint blockade with anti-PD-1 and anti-CTLA-4 antibodies is becoming ...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fnmol.2019.00282

    authors: Lorger M,Andreou T,Fife C,James F

    更新日期:2019-11-21 00:00:00

  • Loss of DEK Expression Induces Alzheimer's Disease Phenotypes in Differentiated SH-SY5Y Cells.

    abstract::Alzheimer's disease (AD) is the most common cause of dementia and is characterized by the buildup of β-amyloid plaques and neurofibrillary Tau tangles. This leads to decreased synaptic efficacy, cell death, and, consequently, brain atrophy in patients. Behaviorally, this manifests as memory loss and confusion. Using a...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2020.594319

    authors: Greene AN,Parks LG,Solomon MB,Privette Vinnedge LM

    更新日期:2020-11-16 00:00:00

  • Excessive Treadmill Training Enhances Brain-Specific MicroRNA-34a in the Mouse Hippocampus.

    abstract::Background: An imbalance between total training load and total recovery may cause overtraining (OT). The purpose of the present study was to verify the effects of OT on the expression of brain-derived neurotrophic factor (BDNF), its receptor tropomyosin receptor kinase B (TrkB) and p75 and the dynamic expression patte...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2020.00007

    authors: Xu L,Zheng YL,Yin X,Xu SJ,Tian D,Zhang CY,Wang S,Ma JZ

    更新日期:2020-01-30 00:00:00

  • Role of Caspase-8 and Fas in Cell Death After Spinal Cord Injury.

    abstract::Spinal cord injury (SCI) causes the death of neurons and glial cells due to the initial mechanical forces (i.e., primary injury) and through a cascade of secondary molecular events (e.g., inflammation or excitotoxicity) that exacerbate cell death. The loss of neurons and glial cells that are not replaced after the inj...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fnmol.2018.00101

    authors: Sobrido-Cameán D,Barreiro-Iglesias A

    更新日期:2018-04-03 00:00:00

  • Therapeutic Potential of Secreted Amyloid Precursor Protein APPsα.

    abstract::Cleavage of the amyloid precursor protein (APP) by α-secretase generates an extracellularly released fragment termed secreted APP-alpha (APPsα). Not only is this process of interest due to the cleavage of APP within the amyloid-beta sequence, but APPsα itself has many physiological properties that suggest its great po...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fnmol.2017.00030

    authors: Mockett BG,Richter M,Abraham WC,Müller UC

    更新日期:2017-02-07 00:00:00

  • Dietary-Induced Signals That Activate the Gonadal Longevity Pathway during Development Regulate a Proteostasis Switch in Caenorhabditis elegans Adulthood.

    abstract::Cell-non-autonomous signals dictate the functional state of cellular quality control systems, remodeling the ability of cells to cope with stress and maintain protein homeostasis (proteostasis). One highly regulated cell-non-autonomous switch controls proteostatic capacity in Caenorhabditis elegans adulthood. Signals ...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2017.00254

    authors: Shemesh N,Meshnik L,Shpigel N,Ben-Zvi A

    更新日期:2017-08-09 00:00:00

  • Post-translational Regulation of GLT-1 in Neurological Diseases and Its Potential as an Effective Therapeutic Target.

    abstract::Glutamate transporter-1 (GLT-1) is a Na+-dependent transporter that plays a key role in glutamate homeostasis by removing excess glutamate in the central nervous system (CNS). GLT-1 dysregulation occurs in various neurological diseases including Huntington's disease (HD), Alzheimer's disease (AD), Parkinson's disease ...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fnmol.2019.00164

    authors: Peterson AR,Binder DK

    更新日期:2019-07-09 00:00:00

  • Transcriptional Reorganization of Drosophila Motor Neurons and Their Muscular Junctions toward a Neuroendocrine Phenotype by the bHLH Protein Dimmed.

    abstract::Neuroendocrine cells store and secrete bulk amounts of neuropeptides, and display morphological and molecular characteristics distinct from neurons signaling with classical neurotransmitters. In Drosophila the transcription factor Dimmed (Dimm), is a prime organizer of neuroendocrine capacity in a majority of the pept...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2017.00260

    authors: Luo J,Liu Y,Nässel DR

    更新日期:2017-08-14 00:00:00

  • Corrigendum: Gap Junctions in A8 Amacrine Cells Are Made of Connexin36 but Are Differently Regulated Than Gap Junctions in AII Amacrine Cells.

    abstract::[This corrects the article DOI: 10.3389/fnmol.2019.00099.]. ...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章,已发布勘误

    doi:10.3389/fnmol.2019.00149

    authors: Yadav SC,Tetenborg S,Dedek K

    更新日期:2019-06-12 00:00:00

  • Engineering a genetically-encoded SHG chromophore by electrostatic targeting to the membrane.

    abstract::Although second harmonic generation (SHG) microscopy provides unique imaging advantages for voltage imaging and other biological applications, genetically-encoded SHG chromophores remain relatively unexplored. SHG only arises from non-centrosymmetric media, so an anisotropic arrangement of chromophores is essential to...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2014.00093

    authors: Jinno Y,Shoda K,Rial-Verde E,Yuste R,Miyawaki A,Tsutsui H

    更新日期:2014-11-27 00:00:00

  • The Role of the Heat Shock Protein B8 (HSPB8) in Motoneuron Diseases.

    abstract::Amyotrophic lateral sclerosis (ALS) and spinal and bulbar muscular atrophy (SBMA) are two motoneuron diseases (MNDs) characterized by aberrant protein behavior in affected cells. In familial ALS (fALS) and in SBMA specific gene mutations lead to the production of neurotoxic proteins or peptides prone to misfold, which...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fnmol.2017.00176

    authors: Rusmini P,Cristofani R,Galbiati M,Cicardi ME,Meroni M,Ferrari V,Vezzoli G,Tedesco B,Messi E,Piccolella M,Carra S,Crippa V,Poletti A

    更新日期:2017-06-21 00:00:00

  • Achaete-Scute Homolog 1 Expression Controls Cellular Differentiation of Neuroblastoma.

    abstract::Neuroblastoma, the major cause of infant cancer deaths, results from fast proliferation of undifferentiated neuroblasts. Treatment of high-risk neuroblastoma includes differentiation with retinoic acid (RA); however, the resistance of many of these tumors to RA-induced differentiation poses a considerable challenge. H...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2016.00156

    authors: Kasim M,Heß V,Scholz H,Persson PB,Fähling M

    更新日期:2016-12-21 00:00:00

  • Alzheimer's Disease: From Genetic Variants to the Distinct Pathological Mechanisms.

    abstract::Being the most common cause of dementia, AD is a polygenic and neurodegenerative disease. Complex and multiple factors have been shown to be involved in its pathogenesis, of which the genetics play an indispensable role. It is widely accepted that discovery of potential genes related to the pathogenesis of AD would be...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fnmol.2017.00319

    authors: Sun Q,Xie N,Tang B,Li R,Shen Y

    更新日期:2017-10-06 00:00:00

  • mRNA Transcriptomics of Galectins Unveils Heterogeneous Organization in Mouse and Human Brain.

    abstract::Background: Galectins, a family of non-classically secreted, β-galactoside binding proteins is involved in several brain disorders; however, no systematic knowledge on the normal neuroanatomical distribution and functions of galectins exits. Hence, the major purpose of this study was to understand spatial distribution...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2016.00139

    authors: John S,Mishra R

    更新日期:2016-12-16 00:00:00

  • Schwann Cell Precursors; Multipotent Glial Cells in Embryonic Nerves.

    abstract::The cells of the neural crest, often referred to as neural crest stem cells, give rise to a number of sub-lineages, one of which is Schwann cells, the glial cells of peripheral nerves. Crest cells transform to adult Schwann cells through the generation of two well defined intermediate stages, the Schwann cell precurso...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fnmol.2019.00069

    authors: Jessen KR,Mirsky R

    更新日期:2019-03-26 00:00:00

  • Alpha2-Containing Glycine Receptors Promote Neonatal Spontaneous Activity of Striatal Medium Spiny Neurons and Support Maturation of Glutamatergic Inputs.

    abstract::Glycine receptors (GlyRs) containing the α2 subunit are highly expressed in the developing brain, where they regulate neuronal migration and maturation, promote spontaneous network activity and subsequent development of synaptic connections. Mutations in GLRA2 are associated with autism spectrum disorder, but the unde...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2018.00380

    authors: Comhair J,Devoght J,Morelli G,Harvey RJ,Briz V,Borrie SC,Bagni C,Rigo JM,Schiffmann SN,Gall D,Brône B,Molchanova SM

    更新日期:2018-10-15 00:00:00

  • Parvalbumin-Neurons of the Ventrolateral Hypothalamic Parvafox Nucleus Receive a Glycinergic Input: A Gene-Microarray Study.

    abstract::The ventrolateral hypothalamic parvafox (formerly called PV1-Foxb1) nucleus is an anatomical entity of recent discovery and unknown function. With a view to gaining an insight into its putative functional role(s), we conducted a gene-microarray analysis and, armed with the forthcoming data, controlled the results with...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2017.00008

    authors: Szabolcsi V,Albisetti GW,Celio MR

    更新日期:2017-01-23 00:00:00

  • The Enzymatic Core of the Parkinson's Disease-Associated Protein LRRK2 Impairs Mitochondrial Biogenesis in Aging Yeast.

    abstract::Mitochondrial dysfunction is a prominent trait of cellular decline during aging and intimately linked to neuronal degeneration during Parkinson's disease (PD). Various proteins associated with PD have been shown to differentially impact mitochondrial dynamics, quality control and function, including the leucine-rich r...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2018.00205

    authors: Aufschnaiter A,Kohler V,Walter C,Tosal-Castano S,Habernig L,Wolinski H,Keller W,Vögtle FN,Büttner S

    更新日期:2018-06-21 00:00:00

  • The Electrophysiological Determinants of Corticospinal Motor Neuron Vulnerability in ALS.

    abstract::The brain is complex and heterogeneous. Even though numerous independent studies indicate cortical hyperexcitability as a potential contributor to amyotrophic lateral sclerosis (ALS) pathology, the mechanisms that are responsible for upper motor neuron (UMN) vulnerability remain elusive. To reveal the electrophysiolog...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2020.00073

    authors: Jara JH,Sheets PL,Nigro MJ,Perić M,Brooks C,Heller DB,Martina M,Andjus PR,Ozdinler PH

    更新日期:2020-05-19 00:00:00

  • EZH2 Is Essential for Fate Determination in the Mammalian Isthmic Area.

    abstract::The polycomb group proteins (PcGs) are a group of epigenetic factors associated with gene silencing. They are found in several families of multiprotein complexes, including polycomb repressive complex 2 (PRC2). EZH2, EED and SUZ12 form the core components of the PRC2 complex, which is responsible for the mono, di- and...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2019.00076

    authors: Wever I,Wagemans CMRJ,Smidt MP

    更新日期:2019-04-09 00:00:00

  • Implications of DNA Methylation in Parkinson's Disease.

    abstract::It has been 200 years since Parkinson's disease (PD) was first described, yet many aspects of its etiopathogenesis remain unclear. PD is a progressive and complex neurodegenerative disorder caused by genetic and environmental factors including aging, nutrition, pesticides and exposure to heavy metals. DNA methylation ...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fnmol.2017.00225

    authors: Miranda-Morales E,Meier K,Sandoval-Carrillo A,Salas-Pacheco J,Vázquez-Cárdenas P,Arias-Carrión O

    更新日期:2017-07-18 00:00:00