TBC1D24, an ARF6-Interacting Protein, Is Mutated in Familial Infantile Myoclonic Epilepsy Antonio Falace, Fabia Filipello, Veronica La Padula, Nicola.

Slides:

Advertisements

Similar presentations

Biphasic Alteration of the Inhibitory Synapse Scaffold Protein Gephyrin in Early and Late Stages of an Alzheimer Disease Model Eva Kiss, Karin Gorgas,

Advertisements

Figure 2. Co-expression of mutant proteins with wt cx26

Okadaic-Acid-Induced Inhibition of Protein Phosphatase 2A Produces Activation of Mitogen-Activated Protein Kinases ERK1/2, MEK1/2, and p70 S6, Similar.

Benign Familial Infantile Convulsions: Mapping of a Novel Locus on Chromosome 2q24 and Evidence for Genetic Heterogeneity Michela Malacarne, Elena Gennaro,

Mapping of a Locus for a Familial Autosomal Recessive Idiopathic Myoclonic Epilepsy of Infancy to Chromosome 16p13 Federico Zara, Elena Gennaro, Mariano.

Motor Protein KIF1A Is Essential for Hippocampal Synaptogenesis and Learning Enhancement in an Enriched Environment Makoto Kondo, Yosuke Takei, Nobutaka.

Federico Dajas-Bailador, Emma V. Jones, Alan J. Whitmarsh

Pericentrosomal Localization of the TIG3 Tumor Suppressor Requires an N-Terminal Hydrophilic Region Motif Tiffany M. Scharadin, Gautam Adhikary, Kristin.

Mutations in AGBL1 Cause Dominant Late-Onset Fuchs Corneal Dystrophy and Alter Protein-Protein Interaction with TCF4 S. Amer Riazuddin, Shivakumar Vasanth,

Volume 82, Issue 1, Pages (April 2014)

A Homozygous Mutation in Human PRICKLE1 Causes an Autosomal-Recessive Progressive Myoclonus Epilepsy-Ataxia Syndrome Alexander G. Bassuk, Robyn H. Wallace,

Eija Siintola, Meral Topcu, Nina Aula, Hannes Lohi, Berge A

Targeted High-Throughput Sequencing Identifies Mutations in atlastin-1 as a Cause of Hereditary Sensory Neuropathy Type I Christian Guelly, Peng-Peng.

Density of dendritic spines on L2/3 pyramidal neurons is greater in visual cortex of germline PirB−/− mice than in PirB+/+ mice at P30. Density of dendritic.

Volume 72, Issue 4, Pages (November 2011)

Molecular Mechanisms Underlying KVS-1-MPS-1 Complex Assembly

Alternative N-Terminal Domains of PSD-95 and SAP97 Govern Activity-Dependent Regulation of Synaptic AMPA Receptor Function Oliver M. Schlüter, Weifeng.

Molecular Therapy - Methods & Clinical Development

Volume 15, Issue 22, Pages (November 2005)

Age-Dependent Decrease in Chaperone Activity Impairs MANF Expression, Leading to Purkinje Cell Degeneration in Inducible SCA17 Mice Su Yang, Shanshan.

Volume 7, Issue 2, Pages (August 2004)

Volume 73, Issue 3, Pages (February 2012)

A Truncating Mutation of TRAPPC9 Is Associated with Autosomal-Recessive Intellectual Disability and Postnatal Microcephaly Ganeshwaran H. Mochida, Muhammad.

Cell-Type-Based Analysis of MicroRNA Profiles in the Mouse Brain

Ovaries and Female Phenotype in a Girl with 46,XY Karyotype and Mutations in the CBX2 Gene Anna Biason-Lauber, Daniel Konrad, Monika Meyer, Carine deBeaufort,

Jungmook Lyu, Vicky Yamamoto, Wange Lu Developmental Cell

BTB/POZ-Zinc Finger Protein Abrupt Suppresses Dendritic Branching in a Neuronal Subtype-Specific and Dosage-Dependent Manner Wenjun Li, Fay Wang, Laurent.

Volume 43, Issue 1, Pages (July 2004)

Volume 31, Issue 1, Pages (July 2001)

Volume 16, Issue 6, Pages (August 2016)

Mutation of Solute Carrier SLC16A12 Associates with a Syndrome Combining Juvenile Cataract with Microcornea and Renal Glucosuria Barbara Kloeckener-Gruissem,

Meilin Wu, James E. Robinson, William J. Joiner Current Biology

Mapping of a Locus for a Familial Autosomal Recessive Idiopathic Myoclonic Epilepsy of Infancy to Chromosome 16p13 Federico Zara, Elena Gennaro, Mariano.

Identification of the Transcriptional Targets of FOXP2, a Gene Linked to Speech and Language, in Developing Human Brain Elizabeth Spiteri, Genevieve.

Homozygous Mutations in WEE2 Cause Fertilization Failure and Female Infertility Qing Sang, Bin Li, Yanping Kuang, Xueqian Wang, Zhihua Zhang, Biaobang.

Volume 18, Issue 11, Pages (March 2017)

Volume 126, Issue 2, Pages (July 2006)

Volume 92, Issue 5, Pages (December 2016)

Autosomal-Dominant Woolly Hair Resulting from Disruption of Keratin 74 (KRT74), a Potential Determinant of Human Hair Texture Yutaka Shimomura, Muhammad.

Exome Sequencing Identifies Autosomal-Dominant SRP72 Mutations Associated with Familial Aplasia and Myelodysplasia Michael Kirwan, Amanda J. Walne, Vincent.

TBC1D24, an ARF6-Interacting Protein, Is Mutated in Familial Infantile Myoclonic Epilepsy Antonio Falace, Fabia Filipello, Veronica La Padula, Nicola.

Jakub M. Swiercz, Rohini Kuner, Jürgen Behrens, Stefan Offermanns

Subregion- and Cell Type–Restricted Gene Knockout in Mouse Brain

Volume 2, Issue 3, Pages (September 2012)

GRM7 Regulates Embryonic Neurogenesis via CREB and YAP

Volume 103, Issue 6, Pages (December 2000)

Volume 12, Issue 4, Pages (April 2007)

Volume 15, Issue 3, Pages (September 2008)

Volume 74, Issue 1, Pages (April 2012)

Volume 92, Issue 6, Pages (December 2016)

A ROP GTPase Signaling Pathway Controls Cortical Microtubule Ordering and Cell Expansion in Arabidopsis Ying Fu, Tongda Xu, Lei Zhu, Mingzhang Wen, Zhenbiao.

Volume 17, Issue 18, Pages (September 2007)

Takashi Hayashi, Gareth M. Thomas, Richard L. Huganir Neuron

Volume 17, Issue 20, Pages (October 2007)

Takashi Hayashi, Gavin Rumbaugh, Richard L. Huganir Neuron

Volume 90, Issue 3, Pages (May 2016)

Atteeq U. Rehman, Regie Lyn P. Santos-Cortez, Robert J

MET/β-catenin complexes during synapse development.

Exome Sequencing Identifies CCDC8 Mutations in 3-M Syndrome, Suggesting that CCDC8 Contributes in a Pathway with CUL7 and OBSL1 to Control Human Growth

Growth Factor-Dependent Trafficking of Cerebellar NMDA Receptors via Protein Kinase B/Akt Phosphorylation of NR2C Bo-Shiun Chen, Katherine W. Roche

Volume 127, Issue 4, Pages (November 2006)

In Vitro Analysis of Huntingtin-Mediated Transcriptional Repression Reveals Multiple Transcription Factor Targets Weiguo Zhai, Hyunkyung Jeong, Libin.

Mutations in NEXN, a Z-Disc Gene, Are Associated with Hypertrophic Cardiomyopathy Hu Wang, Zhaohui Li, Jizheng Wang, Kai Sun, Qiqiong Cui, Lei Song, Yubao.

Destabilization of Cortical Dendrites and Spines by BDNF

Vikram A. Kanda, Anthony Lewis, Xianghua Xu, Geoffrey W. Abbott

Alexandre Irrthum, Marika J

Volume 24, Issue 4, Pages (July 2018)

Volume 72, Issue 4, Pages (November 2011)

A Truncating Mutation of TRAPPC9 Is Associated with Autosomal-Recessive Intellectual Disability and Postnatal Microcephaly Ganeshwaran H. Mochida, Muhammad.

Molecular Therapy - Methods & Clinical Development

Presentation transcript:

TBC1D24, an ARF6-Interacting Protein, Is Mutated in Familial Infantile Myoclonic Epilepsy Antonio Falace, Fabia Filipello, Veronica La Padula, Nicola Vanni, Francesca Madia, Davide De Pietri Tonelli, Fabrizio A. de Falco, Pasquale Striano, Franca Dagna Bricarelli, Carlo Minetti, Fabio Benfenati, Anna Fassio, Federico Zara The American Journal of Human Genetics Volume 87, Issue 3, Pages 365-370 (September 2010) DOI: 10.1016/j.ajhg.2010.07.020 Copyright © 2010 The American Society of Human Genetics Terms and Conditions

Figure 1 Genetic Analysis of TBC1D24 (A) Pedigree of the family with FIME and segregation analysis of TBC1D24 mutations. Haplotypes are shown in colored bars. The red and green haplotypes cosegregate with c.1526C>T and c.439G>C TBC1D24 mutations, respectively. Affected patients are indicated by filled symbols. (B) Electropherograms of c.439G>C and c.1526C>T mutations. (C) Genomic organization and functional domains of human TBC1D24. Affected amino acids are highly conserved throughout evolution. The American Journal of Human Genetics 2010 87, 365-370DOI: (10.1016/j.ajhg.2010.07.020) Copyright © 2010 The American Society of Human Genetics Terms and Conditions

Figure 2 Expression Analysis of TBC1D24 (A) RT-PCR showing the expression profile of TBC1D24 in various human tissues. TBC1D24 is preferentially expressed in brain. Data are represented as means ± SEM. (B) RNA in situ hybridization on brain sections from 12-week-old mouse shows that Tbc1d24 is abundantly expressed in the neocortex (Cx) and hippocampus (Hp). (C) High-magnification image of the cerebral cortex revealed a higher expression of Tbc1d24 in deep cortical layers (V/VI) compared to superficial layers (II-III). (D) High-magnification image of hippocampus shows the highest expression of Tbc1d24 in the CA3 region compared to the CA1 region and dentate gyrus (DG). Hb, hindbrain. The American Journal of Human Genetics 2010 87, 365-370DOI: (10.1016/j.ajhg.2010.07.020) Copyright © 2010 The American Society of Human Genetics Terms and Conditions

Figure 3 TBC1D24 Is an ARF6-Interacting Protein (A) Representative image of a COS-7 cell transfected with GFP-TBC1D24 and visualized 36 hr after transfection. (B) Representative images of a COS-7 cell cotransfected with GFP-TBC1D24 and ARF6-HA and visualized 36 hr after transfection. HA immunoreactivity was detected by HA antibody and Alexa546 conjugated secondary antibodies. The arrow in the merge panel shows colocalization of overexpressed ARF6 and TBC1D24 at the plasma membrane. Scale bars represent 20 μm. (C) TBC1D24-WT, D147H, and A509V were cotransfected with HA-tagged wild-type (WT), T27N, or Q67L ARF6 in COS-7 cells and immunoprecipitated (IP) with GFP antibody. Associated ARF6 (coIP) was detected by HA antibody (αHA) in retrospective western blotting (WB). Wcl, whole cell lysate. The American Journal of Human Genetics 2010 87, 365-370DOI: (10.1016/j.ajhg.2010.07.020) Copyright © 2010 The American Society of Human Genetics Terms and Conditions

Figure 4 Functional Analysis of WT and Mutant TBC1D24 (A) Representative images of mouse cortical neurons transfected at 6 DIV with either GFP, GFP-TBC1D24-wt (WT), GFP-TBC1D24-D147H (D147H), or GFP-TBC1D24-A509V (A509V) and visualized 36 hr after transfection. Scale bar represents 50 μm. (B and C) Overexpression of TBC1D24 provoked a massive increase in neurite length (B) and branching (C), whereas overexpression of its epileptogenic mutants (i.e., D147H and A509V) reverted this phenotype. (D) Quantitative analysis of neurite (total), dendrite, or axon length in 33 cells for each genotype. Dendrites and axons were distinguished by MAP2 labeling and/or morphology. Data expressed as means ± SEM and compared via one-way analysis of variance (ANOVA, B and C) or repeated-measures ANOVA (D) followed by the Bonferroni's multiple comparison test. ∗∗∗p < 0.0001, ∗∗p < 0.001 versus GFP; °°°p < 0.0001, °°p < 0.001, °p < 0.01 versus GFP-TBC1D24-wt. The American Journal of Human Genetics 2010 87, 365-370DOI: (10.1016/j.ajhg.2010.07.020) Copyright © 2010 The American Society of Human Genetics Terms and Conditions