Loss of non-canonical KCC2 functions promotes developmental apoptosis of cortical projection neurons.


:KCC2, encoded in humans by the SLC12A5 gene, is a multifunctional neuron-specific protein initially identified as the chloride (Cl- ) extruder critical for hyperpolarizing GABAA receptor currents. Independently of its canonical function as a K-Cl cotransporter, KCC2 regulates the actin cytoskeleton via molecular interactions mediated through its large intracellular C-terminal domain (CTD). Contrary to the common assumption that embryonic neocortical projection neurons express KCC2 at non-significant levels, here we show that loss of KCC2 enhances apoptosis of late-born upper-layer cortical projection neurons in the embryonic brain. In utero electroporation of plasmids encoding truncated, transport-dead KCC2 constructs retaining the CTD was as efficient as of that encoding full-length KCC2 in preventing elimination of migrating projection neurons upon conditional deletion of KCC2. This was in contrast to the effect of a full-length KCC2 construct bearing a CTD missense mutation (KCC2R952H ), which disrupts cytoskeletal interactions and has been found in patients with neurological and psychiatric disorders, notably seizures and epilepsy. Together, our findings indicate ion transport-independent, CTD-mediated regulation of developmental apoptosis by KCC2 in migrating cortical projection neurons.




EMBO reports


Mavrovic M,Uvarov P,Delpire E,Vutskits L,Kaila K,Puskarjov M




Has Abstract


2020-04-03 00:00:00












  • Characteristics of post-transcriptional gene silencing.

    abstract::A number of gene silencing phenomena that inactivate genes at the post-transcriptional level have been identified. Due to its potential for studying gene function, post-transcriptional gene silencing (PTGS) has become an intense area of research. In this review we describe the different means of inducing PTGS and disc...

    journal_title:EMBO reports

    pub_type: 杂志文章,评审


    authors: Chicas A,Macino G

    更新日期:2001-11-01 00:00:00

  • Organellar proteomics: turning inventories into insights.

    abstract::Subcellular organization is yielding to large-scale analysis. Researchers are now applying robust mass-spectrometry-based proteomics methods to obtain an inventory of biochemically isolated organelles that contain hundreds of proteins. High-resolution methods allow accurate protein identification, and novel algorithms...

    journal_title:EMBO reports

    pub_type: 杂志文章,评审


    authors: Andersen JS,Mann M

    更新日期:2006-09-01 00:00:00

  • Endogenous electric currents might guide rostral migration of neuroblasts.

    abstract::Mechanisms that guide directional migration of neuroblasts from the subventricular zone (SVZ) are not well understood. We report here that endogenous electric currents serve as a guidance cue for neuroblast migration. We identify the existence of naturally occurring electric currents (1.5±0.6 μA/cm(2), average field s...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Cao L,Wei D,Reid B,Zhao S,Pu J,Pan T,Yamoah E,Zhao M

    更新日期:2013-02-01 00:00:00

  • p53 modulates homologous recombination by transcriptional regulation of the RAD51 gene.

    abstract::DNA repair by homologous recombination is involved in maintaining genome stability. Previous data report that wild-type p53 suppresses homologous recombination and physically interacts with Rad51. Here, we show the in vivo binding of wild-type p53 to a p53 response element in the promoter of Rad51 and the downregulati...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Arias-Lopez C,Lazaro-Trueba I,Kerr P,Lord CJ,Dexter T,Iravani M,Ashworth A,Silva A

    更新日期:2006-02-01 00:00:00

  • Phosphorylation of ubiquitin at Ser65 affects its polymerization, targets, and proteome-wide turnover.

    abstract::Ubiquitylation is an essential post-translational modification that regulates numerous cellular processes, most notably protein degradation. Ubiquitin can itself be phosphorylated at nearly every serine, threonine, and tyrosine residue. However, the effect of this modification on ubiquitin function is largely unknown....

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Swaney DL,Rodríguez-Mias RA,Villén J

    更新日期:2015-09-01 00:00:00

  • Epigenome changes in active and inactive polycomb-group-controlled regions.

    abstract::The Polycomb group (PcG) of proteins conveys epigenetic inheritance of repressed transcriptional states. In Drosophila, the Polycomb repressive complex 1 (PRC1) maintains the silent state by inhibiting the transcription machinery and chromatin remodelling at core promoters. Using immunoprecipitation of in vivo formald...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Breiling A,O'Neill LP,D'Eliseo D,Turner BM,Orlando V

    更新日期:2004-10-01 00:00:00

  • Phosphorylation of histone H3 is functionally linked to retinoic acid receptor beta promoter activation.

    abstract::Ligand-dependent transcriptional activation of retinoic acid receptors (RARs) is a multistep process culminating in the formation of a multimeric co-activator complex on regulated promoters. Several co-activator complexes harbor an acetyl transferase activity, which is required for retinoid-induced transcription of re...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Lefebvre B,Ozato K,Lefebvre P

    更新日期:2002-04-01 00:00:00

  • Structural coupling of the EF hand and C-terminal GTPase domains in the mitochondrial protein Miro.

    abstract::Miro is a highly conserved calcium-binding GTPase at the regulatory nexus of mitochondrial transport and autophagy. Here we present crystal structures comprising the tandem EF hand and carboxy terminal GTPase (cGTPase) domains of Drosophila Miro. The structures reveal two previously unidentified 'hidden' EF hands, eac...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Klosowiak JL,Focia PJ,Chakravarthy S,Landahl EC,Freymann DM,Rice SE

    更新日期:2013-11-01 00:00:00

  • Transformation of a neural activation and patterning model.

    abstract::The activation and transformation model of vertebrate nervous system formation posits that neural tissue is initially induced, or activated, with anterior forebrain character. Once established, a subset is then transformed into the more posterior midbrain, hindbrain, and spinal cord by signals emanating from the poste...

    journal_title:EMBO reports

    pub_type: 评论,杂志文章


    authors: Al Anber A,Martin BL

    更新日期:2019-08-01 00:00:00

  • Initiation of epigenetic reprogramming of the X chromosome in somatic nuclei transplanted to a mouse oocyte.

    abstract::The active and inactive X chromosomes have distinct epigenetic marks in somatic nuclei, which undergo reprogramming after transplantation into oocytes. We show that, despite the disappearance of Xist RNA coating in 30 min, the epigenetic memory of the inactive X persists with the precocious appearance of histone H3 tr...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Bao S,Miyoshi N,Okamoto I,Jenuwein T,Heard E,Azim Surani M

    更新日期:2005-08-01 00:00:00

  • PDS5 proteins regulate the length of axial elements and telomere integrity during male mouse meiosis.

    abstract::Cohesin cofactors regulate the loading, maintenance, and release of cohesin complexes from chromosomes during mitosis but little is known on their role during vertebrate meiosis. One such cofactor is PDS5, which exists as two paralogs in somatic and germline cells, PDS5A and PDS5B, with unclear functions. Here, we hav...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Viera A,Berenguer I,Ruiz-Torres M,Gómez R,Guajardo A,Barbero JL,Losada A,Suja JA

    更新日期:2020-06-04 00:00:00

  • Control of histone methylation and genome stability by PTIP.

    abstract::PTIP regulates gene transcription by controlling the methylation of histone H3, and also has important roles in cellular responses to DNA damage or to perturbed DNA replication. The available data suggest that the functions of PTIP in transcription and preserving genome stability might be independent and mediated by f...

    journal_title:EMBO reports

    pub_type: 杂志文章,评审


    authors: Muñoz IM,Rouse J

    更新日期:2009-03-01 00:00:00

  • The Ark1/Prk1 family of protein kinases. Regulators of endocytosis and the actin skeleton.

    abstract::The Ark/Prk serine/threonine kinases initiate phosphorylation cycles that control the endocytic machinery in mammalian cells and in yeast, and the actin cytoskeleton in yeast. The members of this protein family are unified by homologies in their kinase domain, but are generally diverse in their other domains. The evol...

    journal_title:EMBO reports

    pub_type: 杂志文章,评审


    authors: Smythe E,Ayscough KR

    更新日期:2003-03-01 00:00:00

  • Extracellular vesicles deliver Mycobacterium RNA to promote host immunity and bacterial killing.

    abstract::Extracellular vesicles (EVs) have been shown to carry microbial components and function in the host defense against infections. In this study, we demonstrate that Mycobacterium tuberculosis (M.tb) RNA is delivered into macrophage-derived EVs through an M.tb SecA2-dependent pathway and that EVs released from M.tb-infec...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Cheng Y,Schorey JS

    更新日期:2019-03-01 00:00:00

  • Comment on "Close loop peer review" by Michael Hill.

    abstract::Comment on "Close loop peer review" by Michael Hill. ...

    journal_title:EMBO reports

    pub_type: 评论,信件


    authors: Horowitz A

    更新日期:2019-08-01 00:00:00

  • Mitophagy regulates integrity of mitochondria at synapses and is critical for synaptic maintenance.

    abstract::Synaptic mitochondria are particularly vulnerable to physiological insults, and defects in synaptic mitochondria are linked to early pathophysiology of Alzheimer's disease (AD). Mitophagy, a cargo-specific autophagy for elimination of dysfunctional mitochondria, constitutes a key quality control mechanism. However, ho...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Han S,Jeong YY,Sheshadri P,Su X,Cai Q

    更新日期:2020-09-03 00:00:00

  • Priming the nucleosome: a role for HMGB proteins?

    abstract::The high-mobility-group B (HMGB) chromosomal proteins are characterized by the HMG box, a DNA-binding domain that both introduces a tight bend into DNA and binds preferentially to a variety of distorted DNA structures. The HMGB proteins seem to act primarily as architectural facilitators in the manipulation of nucleop...

    journal_title:EMBO reports

    pub_type: 杂志文章,评审


    authors: Travers AA

    更新日期:2003-02-01 00:00:00

  • Potent degradation of neuronal miRNAs induced by highly complementary targets.

    abstract::MicroRNAs (miRNAs) regulate target mRNAs by silencing them. Reciprocally, however, target mRNAs can also modulate miRNA stability. Here, we uncover a remarkable efficacy of target RNA-directed miRNA degradation (TDMD) in rodent primary neurons. Coincident with degradation, and while still bound to Argonaute, targeted ...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: de la Mata M,Gaidatzis D,Vitanescu M,Stadler MB,Wentzel C,Scheiffele P,Filipowicz W,Großhans H

    更新日期:2015-04-01 00:00:00

  • The 3.7 A projection map of the glycerol facilitator GlpF: a variant of the aquaporin tetramer.

    abstract::GlpF, the glycerol facilitator protein of Escherichia coli, is an archetypal member of the aquaporin superfamily. To assess its structure, recombinant histidine-tagged protein was overexpressed, solubilized in octylglucoside and purified to homogeneity. Negative stain electron microscopy of solubilized GlpF protein re...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Braun T,Philippsen A,Wirtz S,Borgnia MJ,Agre P,Kühlbrandt W,Engel A,Stahlberg H

    更新日期:2000-08-01 00:00:00

  • Towards restoring proper chromosome segregation and preventing ageing.

    abstract::The natural progressive dysfunction of most living organisms-ageing-has captured the attention of several studies, with the intention to develop rejuvenation strategies. Evidence is emerging of a positive correlation between natural ageing and chromosomal instability (CIN). In this issue of EMBO Reports, Barroso-Vilar...

    journal_title:EMBO reports

    pub_type: 评论,新闻


    authors: Tovini L,McClelland SE

    更新日期:2020-05-06 00:00:00

  • Yarrowia lipolytica Pex20p, Saccharomyces cerevisiae Pex18p/Pex21p and mammalian Pex5pL fulfil a common function in the early steps of the peroxisomal PTS2 import pathway.

    abstract::Import of peroxisomal matrix proteins is essential for peroxisome biogenesis. Genetic and biochemical studies using a variety of different model systems have led to the discovery of 23 PEX genes required for this process. Although it is generally believed that, in contrast to mitochondria and chloroplasts, translocati...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Einwächter H,Sowinski S,Kunau WH,Schliebs W

    更新日期:2001-11-01 00:00:00

  • EphrinB2/EphB4 signaling regulates non-sprouting angiogenesis by VEGF.

    abstract::Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis, whose best-understood mechanism is sprouting. However, therapeutic VEGF delivery to ischemic muscle induces angiogenesis by the alternative process of intussusception, or vascular splitting, whose molecular regulation is essentially unk...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Groppa E,Brkic S,Uccelli A,Wirth G,Korpisalo-Pirinen P,Filippova M,Dasen B,Sacchi V,Muraro MG,Trani M,Reginato S,Gianni-Barrera R,Ylä-Herttuala S,Banfi A

    更新日期:2018-05-01 00:00:00

  • Secured cutting: controlling separase at the metaphase to anaphase transition.

    abstract::The final irreversible step in the duplication and distribution of genomes to daughter cells takes place at the metaphase to anaphase transition. At this point aligned sister chromatid pairs split and separate. During metaphase, cohesion between sister chromatids is maintained by the chromosomal multi-subunit cohesin ...

    journal_title:EMBO reports

    pub_type: 杂志文章,评审


    authors: Uhlmann F

    更新日期:2001-06-01 00:00:00

  • Helicase89B is a Mot1p/BTAF1 homologue that mediates an antimicrobial response in Drosophila.

    abstract::We have identified a novel component, Helicase89B, that is required for the inducible antimicrobial response in Drosophila larvae by means of a P-element insertional genetic screen. Helicase89B belongs to the Mot1p/BTAF1 subfamily of SNF2-like ATPases. This subfamily can interact with TATA-binding proteins, but whethe...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Yagi Y,Ip YT

    更新日期:2005-11-01 00:00:00

  • The Methanobacterium thermoautotrophicum MCM protein can form heptameric rings.

    abstract::Mini-chromosome maintenance (MCM) proteins form a conserved family found in all eukaryotes and are essential for DNA replication. They exist as heteromultimeric complexes containing as many as six different proteins. These complexes are believed to be the replicative helicases, functioning as hexameric rings at replic...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Yu X,VanLoock MS,Poplawski A,Kelman Z,Xiang T,Tye BK,Egelman EH

    更新日期:2002-08-01 00:00:00

  • Werner's syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest.

    abstract::Individuals affected by the autosomal recessive disorder Werner's syndrome (WS) develop many of the symptoms characteristic of premature ageing. Primary fibroblasts cultured from WS patients exhibit karyotypic abnormalities and a reduced replicative life span. The WRN gene encodes a 3'-5' DNA helicase, and is a member...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Constantinou A,Tarsounas M,Karow JK,Brosh RM,Bohr VA,Hickson ID,West SC

    更新日期:2000-07-01 00:00:00

  • Phosphorylation of the Stat1 transactivating domain is required for the response to type I interferons.

    abstract::Stat1 (signal transducer and activator of transcription 1) regulates transcription in response to the type I interferons IFN-alpha and IFN-beta, either in its dimerized form or as a subunit of the interferon-stimulated gene factor 3 (Isgf3) complex (consisting of Stat1, Stat2 and interferon-regulating factor 9). Full-...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Pilz A,Ramsauer K,Heidari H,Leitges M,Kovarik P,Decker T

    更新日期:2003-04-01 00:00:00

  • A matter of choice: the establishment of sister chromatid cohesion.

    abstract::Sister chromatid cohesion is the basis for the recognition of chromosomal DNA replication products for their bipolar segregation in mitosis. Fundamental to sister chromatid cohesion is the ring-shaped cohesin complex, which is loaded onto chromosomes long before the initiation of DNA replication and is thought to hold...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Uhlmann F

    更新日期:2009-10-01 00:00:00

  • Yeast caspase 1 links messenger RNA stability to apoptosis in yeast.

    abstract::During the past years, yeasts have been successfully established as models to study the mechanisms of apoptotic regulation. We recently showed that mutations in the LSM4 gene, which is involved in messenger RNA decapping, lead to increased mRNA stability and apoptosis in yeast. Here, we show that mitochondrial functio...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Mazzoni C,Herker E,Palermo V,Jungwirth H,Eisenberg T,Madeo F,Falcone C

    更新日期:2005-11-01 00:00:00

  • E2F1 is crucial for E2F-dependent apoptosis.

    abstract::Loss of the retinoblastoma protein, pRB, leads to apoptosis, and several results have suggested that this is dependent on the E2F transcription factors. However, so far, the ability of the different E2F family members to contribute to apoptosis is controversial. Here, we show that ectopic expression of E2F3 results in...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Lazzerini Denchi E,Helin K

    更新日期:2005-07-01 00:00:00