Synaptotagmin 2 Is the Fast Ca2+ Sensor at a Central Inhibitory Synapse.

Abstract:

:GABAergic synapses in brain circuits generate inhibitory output signals with submillisecond latency and temporal precision. Whether the molecular identity of the release sensor contributes to these signaling properties remains unclear. Here, we examined the Ca2+ sensor of exocytosis at GABAergic basket cell (BC) to Purkinje cell (PC) synapses in cerebellum. Immunolabeling suggested that BC terminals selectively expressed synaptotagmin 2 (Syt2), whereas synaptotagmin 1 (Syt1) was enriched in excitatory terminals. Genetic elimination of Syt2 reduced action potential-evoked release to ∼10%, identifying Syt2 as the major Ca2+ sensor at BC-PC synapses. Differential adenovirus-mediated rescue revealed that Syt2 triggered release with shorter latency and higher temporal precision and mediated faster vesicle pool replenishment than Syt1. Furthermore, deletion of Syt2 severely reduced and delayed disynaptic inhibition following parallel fiber stimulation. Thus, the selective use of Syt2 as release sensor at BC-PC synapses ensures fast and efficient feedforward inhibition in cerebellar microcircuits.

journal_name

Cell Rep

journal_title

Cell reports

authors

Chen C,Arai I,Satterfield R,Young SM Jr,Jonas P

doi

10.1016/j.celrep.2016.12.067

subject

Has Abstract

pub_date

2017-01-17 00:00:00

pages

723-736

issue

3

issn

2211-1247

pii

S2211-1247(16)31774-0

journal_volume

18

pub_type

杂志文章
  • Molecular basis for the ribosome functioning as an L-tryptophan sensor.

    abstract::Elevated levels of the free amino acid L-tryptophan (L-Trp) trigger expression of the tryptophanase tnaCAB operon in E. coli. Activation depends on tryptophan-dependent ribosomal stalling during translation of the upstream TnaC peptide. Here, we present a cryoelectron microscopy (cryo-EM) reconstruction at 3.8 Å resol...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2014.09.011

    authors: Bischoff L,Berninghausen O,Beckmann R

    更新日期:2014-10-23 00:00:00

  • Naproxen Exhibits Broad Anti-influenza Virus Activity in Mice by Impeding Viral Nucleoprotein Nuclear Export.

    abstract::Naproxen is a non-steroidal anti-inflammatory drug that has previously been shown to exert antiviral activity against influenza A virus by inhibiting nucleoprotein (NP) binding to RNA. Here, we show that naproxen is a potential broad, multi-mechanistic anti-influenza virus therapeutic, as it inhibits influenza B virus...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2019.04.053

    authors: Zheng W,Fan W,Zhang S,Jiao P,Shang Y,Cui L,Mahesutihan M,Li J,Wang D,Gao GF,Sun L,Liu W

    更新日期:2019-05-07 00:00:00

  • Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication Forks.

    abstract::Replication of a damaged DNA template can threaten the integrity of the genome, requiring the use of various mechanisms to tolerate DNA lesions. The Smc5/6 complex, together with the Nse2/Mms21 SUMO ligase, plays essential roles in genome stability through undefined tasks at damaged replication forks. Various subunits...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2019.10.123

    authors: Zapatka M,Pociño-Merino I,Heluani-Gahete H,Bermúdez-López M,Tarrés M,Ibars E,Solé-Soler R,Gutiérrez-Escribano P,Apostolova S,Casas C,Aragon L,Wellinger R,Colomina N,Torres-Rosell J

    更新日期:2019-12-03 00:00:00

  • Defining midbrain dopaminergic neuron diversity by single-cell gene expression profiling.

    abstract::Effective approaches to neuropsychiatric disorders require detailed understanding of the cellular composition and circuitry of the complex mammalian brain. Here, we present a paradigm for deconstructing the diversity of neurons defined by a specific neurotransmitter using a microfluidic dynamic array to simultaneously...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2014.10.008

    authors: Poulin JF,Zou J,Drouin-Ouellet J,Kim KY,Cicchetti F,Awatramani RB

    更新日期:2014-11-06 00:00:00

  • Plexin B2 Is a Regulator of Monocyte Apoptotic Cell Disassembly.

    abstract::Billions of cells undergo apoptosis daily and often fragment into small, membrane-bound extracellular vesicles termed apoptotic bodies (ApoBDs). We demonstrate that apoptotic monocytes undergo a highly coordinated disassembly process and form long, beaded protrusions (coined as beaded apoptopodia), which fragment to r...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2019.10.014

    authors: Atkin-Smith GK,Miles MA,Tixeira R,Lay FT,Duan M,Hawkins CJ,Phan TK,Paone S,Mathivanan S,Hulett MD,Chen W,Poon IKH

    更新日期:2019-11-12 00:00:00

  • TrxG Complex Catalytic and Non-catalytic Activity Play Distinct Roles in Pancreas Progenitor Specification and Differentiation.

    abstract::Appropriate regulation of genes that coordinate pancreas progenitor proliferation and differentiation is required for pancreas development. Here, we explore the role of H3K4 methylation and the Trithorax group (TrxG) complexes in mediating gene expression during pancreas development. Disruption of TrxG complex assembl...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2019.07.035

    authors: Campbell SA,McDonald CL,Krentz NAJ,Lynn FC,Hoffman BG

    更新日期:2019-08-13 00:00:00

  • Lysine succinylation is a frequently occurring modification in prokaryotes and eukaryotes and extensively overlaps with acetylation.

    abstract::Recent studies have shown that lysines can be posttranslationally modified by various types of acylations. However, except for acetylation, very little is known about their scope and cellular distribution. We mapped thousands of succinylation sites in bacteria (E. coli), yeast (S. cerevisiae), human (HeLa) cells, and ...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2013.07.024

    authors: Weinert BT,Schölz C,Wagner SA,Iesmantavicius V,Su D,Daniel JA,Choudhary C

    更新日期:2013-08-29 00:00:00

  • Dynorphin Controls the Gain of an Amygdalar Anxiety Circuit.

    abstract::Kappa opioid receptors (KORs) are involved in a variety of aversive behavioral states, including anxiety. To date, a circuit-based mechanism for KOR-driven anxiety has not been described. Here, we show that activation of KORs inhibits glutamate release from basolateral amygdala (BLA) inputs to the bed nucleus of the s...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2016.02.069

    authors: Crowley NA,Bloodgood DW,Hardaway JA,Kendra AM,McCall JG,Al-Hasani R,McCall NM,Yu W,Schools ZL,Krashes MJ,Lowell BB,Whistler JL,Bruchas MR,Kash TL

    更新日期:2016-03-29 00:00:00

  • Astroglial-Mediated Remodeling of the Interhemispheric Midline Is Required for the Formation of the Corpus Callosum.

    abstract::The corpus callosum is the major axon tract that connects and integrates neural activity between the two cerebral hemispheres. Although ∼1:4,000 children are born with developmental absence of the corpus callosum, the primary etiology of this condition remains unknown. Here, we demonstrate that midline crossing of cal...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2016.09.033

    authors: Gobius I,Morcom L,Suárez R,Bunt J,Bukshpun P,Reardon W,Dobyns WB,Rubenstein JL,Barkovich AJ,Sherr EH,Richards LJ

    更新日期:2016-10-11 00:00:00

  • PTPMT1 Inhibition Lowers Glucose through Succinate Dehydrogenase Phosphorylation.

    abstract::Virtually all organisms seek to maximize fitness by matching fuel availability with energy expenditure. In vertebrates, glucose homeostasis is central to this process, with glucose levels finely tuned to match changing energy requirements. To discover new pathways regulating glucose levels in vivo, we performed a larg...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2015.01.010

    authors: Nath AK,Ryu JH,Jin YN,Roberts LD,Dejam A,Gerszten RE,Peterson RT

    更新日期:2015-02-10 00:00:00

  • Telomere Recognition and Assembly Mechanism of Mammalian Shelterin.

    abstract::Shelterin is a six-subunit protein complex that plays crucial roles in telomere length regulation, protection, and maintenance. Although several shelterin subunits have been studied in vitro, the biochemical properties of the fully assembled shelterin complex are not well defined. Here, we characterize shelterin using...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2016.12.005

    authors: Erdel F,Kratz K,Willcox S,Griffith JD,Greene EC,de Lange T

    更新日期:2017-01-03 00:00:00

  • HNF4α Combinatorial Isoform Heterodimers Activate Distinct Gene Targets that Differ from Their Corresponding Homodimers.

    abstract::Hepatocyte nuclear factor 4α (HNF4α) is a dimeric transcription factor that controls as much as 60% of all liver genes. However, how it achieves such broad functional diversity is unknown. Here, we show that inflammation and immune pathway genes are differentially regulated in an isoform-dependent manner, confirming t...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2019.02.033

    authors: Ko HL,Zhuo Z,Ren EC

    更新日期:2019-03-05 00:00:00

  • Regulation of Autocrine Signaling in Subsets of Sympathetic Neurons Has Regional Effects on Tissue Innervation.

    abstract::The regulation of innervation by target-derived factors like nerve growth factor (NGF) is the cornerstone of neurotrophic theory. Whereas autocrine signaling in neurons affecting survival and axon growth has been described, it is difficult to reconcile autocrine signaling with the idea that targets control their inner...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2015.02.016

    authors: McWilliams TG,Howard L,Wyatt S,Davies AM

    更新日期:2015-03-10 00:00:00

  • The touch dome defines an epidermal niche specialized for mechanosensory signaling.

    abstract::In mammalian skin, Merkel cells are mechanoreceptor cells that are required for the perception of gentle touch. Recent evidence indicates that mature Merkel cells descend from the proliferative layer of skin epidermis; however, the stem cell niche for Merkel cell homeostasis has not been reported. Here, we provide gen...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2013.04.026

    authors: Doucet YS,Woo SH,Ruiz ME,Owens DM

    更新日期:2013-06-27 00:00:00

  • Mpn1, mutated in poikiloderma with neutropenia protein 1, is a conserved 3'-to-5' RNA exonuclease processing U6 small nuclear RNA.

    abstract::Clericuzio-type poikiloderma with neutropenia (PN) is a rare genodermatosis associated with mutations in the C16orf57 gene, which codes for the uncharacterized protein hMpn1. We show here that, in both fission yeasts and humans, Mpn1 processes the spliceosomal U6 small nuclear RNA (snRNA) posttranscriptionally. In Mpn...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2012.08.031

    authors: Shchepachev V,Wischnewski H,Missiaglia E,Soneson C,Azzalin CM

    更新日期:2012-10-25 00:00:00

  • Identification and Structure of a Multidonor Class of Head-Directed Influenza-Neutralizing Antibodies Reveal the Mechanism for Its Recurrent Elicitation.

    abstract::Multidonor antibodies are of interest for vaccine design because they can in principle be elicited in the general population by a common set of immunogens. For influenza, multidonor antibodies have been observed against the hemagglutinin (HA) stem, but not the immunodominant HA head. Here, we identify and characterize...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2020.108088

    authors: Cheung CS,Fruehwirth A,Paparoditis PCG,Shen CH,Foglierini M,Joyce MG,Leung K,Piccoli L,Rawi R,Silacci-Fregni C,Tsybovsky Y,Verardi R,Wang L,Wang S,Yang ES,Zhang B,Zhang Y,Chuang GY,Corti D,Mascola JR,Shapiro L,K

    更新日期:2020-09-01 00:00:00

  • Lineage-Specific and Non-specific Cytokine-Sensing Genes Respond Differentially to the Master Regulator STAT5.

    abstract::STAT5, a member of the family of signal transducers and activators of transcription, senses cytokines and controls the biology of cell lineages, including mammary, liver, and T cells. Here, we show that STAT5 activates lineage-specific and widely expressed genes through different mechanisms. STAT5 preferentially binds...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2016.11.079

    authors: Zeng X,Willi M,Shin HY,Hennighausen L,Wang C

    更新日期:2016-12-20 00:00:00

  • PHB3 Maintains Root Stem Cell Niche Identity through ROS-Responsive AP2/ERF Transcription Factors in Arabidopsis.

    abstract::The root stem cell niche, which is composed of four mitotically inactive quiescent center (QC) cells and the surrounding actively divided stem cells in Arabidopsis, is critical for growth and root development. Here, we demonstrate that the Arabidopsis prohibitin protein PHB3 is required for the maintenance of root ste...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2017.12.105

    authors: Kong X,Tian H,Yu Q,Zhang F,Wang R,Gao S,Xu W,Liu J,Shani E,Fu C,Zhou G,Zhang L,Zhang X,Ding Z

    更新日期:2018-01-30 00:00:00

  • Discovery and Function of a General Core Hormetic Stress Response in E. coli Induced by Sublethal Concentrations of Antibiotics.

    abstract::A better understanding of the impact of antibiotics on bacteria is required to increase the efficiency of antibiotic treatments and to slow the emergence of resistance. Using Escherichia coli, we examined how bacteria exposed to sublethal concentrations of ampicillin adjust gene expression patterns and metabolism to s...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2016.09.001

    authors: Mathieu A,Fleurier S,Frénoy A,Dairou J,Bredeche MF,Sanchez-Vizuete P,Song X,Matic I

    更新日期:2016-09-27 00:00:00

  • A targeted oligonucleotide enhancer of SMN2 exon 7 splicing forms competing quadruplex and protein complexes in functional conditions.

    abstract::The use of oligonucleotides to activate the splicing of selected exons is limited by a poor understanding of the mechanisms affected. A targeted bifunctional oligonucleotide enhancer of splicing (TOES) anneals to SMN2 exon 7 and carries an exonic splicing enhancer (ESE) sequence. We show that it stimulates splicing sp...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2014.08.051

    authors: Smith LD,Dickinson RL,Lucas CM,Cousins A,Malygin AA,Weldon C,Perrett AJ,Bottrill AR,Searle MS,Burley GA,Eperon IC

    更新日期:2014-10-09 00:00:00

  • BORC Functions Upstream of Kinesins 1 and 3 to Coordinate Regional Movement of Lysosomes along Different Microtubule Tracks.

    abstract::The multiple functions of lysosomes are critically dependent on their ability to undergo bidirectional movement along microtubules between the center and the periphery of the cell. Centrifugal and centripetal movement of lysosomes is mediated by kinesin and dynein motors, respectively. We recently described a multi-su...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2016.10.062

    authors: Guardia CM,Farías GG,Jia R,Pu J,Bonifacino JS

    更新日期:2016-11-15 00:00:00

  • Systematic Kinase Inhibitor Profiling Identifies CDK9 as a Synthetic Lethal Target in NUT Midline Carcinoma.

    abstract::Kinase inhibitors represent the backbone of targeted cancer therapy, yet only a limited number of oncogenic drivers are directly druggable. By interrogating the activity of 1,505 kinase inhibitors, we found that BRD4-NUT-rearranged NUT midline carcinoma (NMC) cells are specifically killed by CDK9 inhibition (CDK9i) an...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2017.08.082

    authors: Brägelmann J,Dammert MA,Dietlein F,Heuckmann JM,Choidas A,Böhm S,Richters A,Basu D,Tischler V,Lorenz C,Habenberger P,Fang Z,Ortiz-Cuaran S,Leenders F,Eickhoff J,Koch U,Getlik M,Termathe M,Sallouh M,Greff Z,Varga Z

    更新日期:2017-09-19 00:00:00

  • MYO6 Regulates Spatial Organization of Signaling Endosomes Driving AKT Activation and Actin Dynamics.

    abstract::APPL1- and RAB5-positive signaling endosomes play a crucial role in the activation of AKT in response to extracellular stimuli. Myosin VI (MYO6) and two of its cargo adaptor proteins, GIPC and TOM1/TOM1L2, localize to these peripheral endosomes and mediate endosome association with cortical actin filaments. Loss of MY...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2017.05.048

    authors: Masters TA,Tumbarello DA,Chibalina MV,Buss F

    更新日期:2017-06-06 00:00:00

  • FOXO/DAF-16 Activation Slows Down Turnover of the Majority of Proteins in C. elegans.

    abstract::Most aging hypotheses assume the accumulation of damage, resulting in gradual physiological decline and, ultimately, death. Avoiding protein damage accumulation by enhanced turnover should slow down the aging process and extend the lifespan. However, lowering translational efficiency extends rather than shortens the l...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2016.07.088

    authors: Dhondt I,Petyuk VA,Cai H,Vandemeulebroucke L,Vierstraete A,Smith RD,Depuydt G,Braeckman BP

    更新日期:2016-09-13 00:00:00

  • NS5A Promotes Constitutive Degradation of IP3R3 to Counteract Apoptosis Induced by Hepatitis C Virus.

    abstract::FBXL2 targets IP3R3 for ubiquitin-mediated degradation to limit Ca2+ flux to mitochondria and, consequently, apoptosis. Efficient replication of hepatitis C virus (HCV) requires geranylgeranylation of FBXL2. Here, we show that the viral protein NS5A forms a trimeric complex with IP3R3 and FBXL2, unmasking IP3R3's degr...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2018.09.088

    authors: Kuchay S,Saeed M,Giorgi C,Li J,Hoffmann HH,Pinton P,Rice CM,Pagano M

    更新日期:2018-10-23 00:00:00

  • The GTPase Rab43 Controls the Anterograde ER-Golgi Trafficking and Sorting of GPCRs.

    abstract::G-protein-coupled receptors (GPCRs) constitute the largest superfamily of cell-surface signaling proteins. However, mechanisms underlying their surface targeting and sorting are poorly understood. Here, we screen the Rab family of small GTPases in the surface transport of multiple GPCRs. We find that manipulation of R...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2017.10.011

    authors: Li C,Wei Z,Fan Y,Huang W,Su Y,Li H,Dong Z,Fukuda M,Khater M,Wu G

    更新日期:2017-10-24 00:00:00

  • Selective Vulnerability of Cancer Cells by Inhibition of Ca(2+) Transfer from Endoplasmic Reticulum to Mitochondria.

    abstract::In the absence of low-level ER-to-mitochondrial Ca(2+) transfer, ATP levels fall, and AMPK-dependent, mTOR-independent autophagy is induced as an essential survival mechanism in many cell types. Here, we demonstrate that tumorigenic cancer cell lines, transformed primary human fibroblasts, and tumors in vivo respond s...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2016.02.030

    authors: Cárdenas C,Müller M,McNeal A,Lovy A,Jaňa F,Bustos G,Urra F,Smith N,Molgó J,Diehl JA,Ridky TW,Foskett JK

    更新日期:2016-03-15 00:00:00

  • Diverse Long RNAs Are Differentially Sorted into Extracellular Vesicles Secreted by Colorectal Cancer Cells.

    abstract::The regulation and functional roles of secreted coding and long noncoding RNAs (lncRNAs; >200 nt) are largely unknown. We previously showed that mutant KRAS colorectal cancer (CRC) cells release extracellular vesicles (EVs) containing distinct proteomes, microRNAs (miRNAs), and circular RNAs. Here, we comprehensively ...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2018.09.054

    authors: Hinger SA,Cha DJ,Franklin JL,Higginbotham JN,Dou Y,Ping J,Shu L,Prasad N,Levy S,Zhang B,Liu Q,Weaver AM,Coffey RJ,Patton JG

    更新日期:2018-10-16 00:00:00

  • Adipocyte Fatty Acid Transfer Supports Megakaryocyte Maturation.

    abstract::Megakaryocytes (MKs) come from a complex process of hematopoietic progenitor maturation within the bone marrow that gives rise to de novo circulating platelets. Bone marrow microenvironment contains a large number of adipocytes with a still ill-defined role. This study aims to analyze the influence of adipocytes and i...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2020.107875

    authors: Valet C,Batut A,Vauclard A,Dortignac A,Bellio M,Payrastre B,Valet P,Severin S

    更新日期:2020-07-07 00:00:00

  • Evolutionary Differences in the Vegf/Vegfr Code Reveal Organotypic Roles for the Endothelial Cell Receptor Kdr in Developmental Lymphangiogenesis.

    abstract::Lymphatic vascular development establishes embryonic and adult tissue fluid balance and is integral in disease. In diverse vertebrate organs, lymphatic vessels display organotypic function and develop in an organ-specific manner. In all settings, developmental lymphangiogenesis is considered driven by vascular endothe...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2019.07.055

    authors: Vogrin AJ,Bower NI,Gunzburg MJ,Roufail S,Okuda KS,Paterson S,Headey SJ,Stacker SA,Hogan BM,Achen MG

    更新日期:2019-08-20 00:00:00