Prof Josef Kittler

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Name: Josef Kittler Email: j.kittler@ucl.ac.uk
Title: Prof Tel: 020 7679 3218
Department: Neuro, Physiology & Pharmacology Fax:
Position: Professor of Molecular Neurobiology Address: Physiology, Medical Sciences Building, UCL South Cloisters, Gower St, London, WC1E 6BT
Research Domain: Basic Life Sciences, Biomedical Imaging (Frontier Disciplines), Genetics (Frontier Disciplines), Nanotechnology (Frontier Disciplines), Neuroscience Web Page: Personal Web Page

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Research Description

Overview Nerve cells in the brain have a highly spatially diverse cellular and subcellular architecture including axon, cell body, and dendrites as major cellular compartments, in addition to subcellular membrane microdomains such as spines, synapses and the secretory and endosomal networks. To ensure efficient signaling between neurons, and to ensure that the correct levels of neuronal network activity are maintained, it is critical that mechanisms exist to tightly regulate the selective transport and localisation of ion channels, receptors and organelles to specific neuronal locations. We are interested in understanding the contribution played by intracellular transport and membrane trafficking of channels, transporters and organelles in regulating the formation, activity and plasticity of synapses. We focus on three major research themes: Firstly, we are studying the molecular and cellular mechanisms regulating the function and membrane trafficking of neurotransmitter receptors (with a particular focus on GABA-A receptors) and transporters and the role this plays in controlling synaptic transmission and the levels of neuronal excitability in the brain. We are similarly interested in how the function of synapses can be controlled by the regulated trafficking of organelles such as mitochondria. Secondly, we concentrate on how intracellular transport is regulated by post-translational modifications (such as phosphorylation, palmitoylation and ubiquitination) and signalling pathways that alter intracellular calcium levels. Thirdly, we wish to understand better how the trafficking of receptors, transporters and other cargo may be altered in neurological and neuropsychiatric diseases including Parkinson's, Alzheimer's and Huntington's diseases, autism and schizophrenia. We combine the use of various techniques, including molecular and cell biology, protein biochemistry, patch clamp electrophysiology, neuronal transfection, and fixed and live cell confocal and CCD imaging. We also use fluorescent protein and Quantum Dot labeling approaches to study the membrane dynamics, localisation and trafficking of proteins and organelles of interest.


Research Activities

Education Description

UCL Collaborators

External Collaborators

Publications

    2014

    • Birsa N, Norkett R, Wauer T, Mevissen TE, Wu HC, Foltynie T, Bhatia K, Hirst WD, Komander D, Plun-Favreau H, Kittler JT (2014). K27 ubiquitination of the mitochondrial transport protein Miro is dependent on serine 65 of the Parkin ubiquitin ligase.. J Biol Chem, , - . doi:10.1074/jbc.M114.563031
    • Pathania M, Davenport EC, Muir J, Sheehan DF, López-Doménech G, Kittler JT (2014). The autism and schizophrenia associated gene CYFIP1 is critical for the maintenance of dendritic complexity and the stabilization of mature spines.. Transl Psychiatry, 4, e374 - . doi:10.1038/tp.2014.16
    • Muir J, Kittler JT (2014). Plasticity of GABAA receptor diffusion dynamics at the axon initial segment.. Front Cell Neurosci, 8, 151 - . doi:10.3389/fncel.2014.00151

    2013

    • Birsa N, Norkett R, Higgs N, Lopez-Domenech G, Kittler JT (2013). Mitochondrial trafficking in neurons and the role of the Miro family of GTPase proteins.. Biochem Soc Trans, 41(6), 1525 - 1531. doi:10.1042/BST20130234
    • Duffney LJ, Wei J, Cheng J, Liu W, Smith KR, Kittler JT, Yan Z (2013). Shank3 Deficiency Induces NMDA Receptor Hypofunction via an Actin-Dependent Mechanism.. J Neurosci, 33(40), 15767 - 15778. doi:10.1523/JNEUROSCI.1175-13.2013

    2012

    • Smith KR, Muir J, Rao Y, Browarski M, Gruenig MC, Sheehan DF, Haucke V, Kittler JT (2012). Stabilization of GABA(A) receptors at endocytic zones is mediated by an AP2 binding motif within the GABA(A) receptor β3 subunit.. J Neurosci, 32(7), 2485 - 2498. doi:10.1523/JNEUROSCI.1622-11.2011
    • Atkin TA, Brandon NJ, Kittler JT (2012). Disrupted in Schizophrenia 1 forms pathological aggresomes that disrupt its function in intracellular transport.. Hum Mol Genet, 21(9), 2017 - 2028. doi:10.1093/hmg/dds018
    • Gruar RI, Tighe CJ, Muir J, Kittler JT, Wojdak M, Kenyon AJ, Darr JA (2012). Continuous hydrothermal synthesis of surface-functionalised nanophosphors for biological imaging. RSC Advances, 2, 10037 - 10047. doi:10.1039/c2ra21798h

    2011

    • Atkin TA, Macaskill AF, Brandon NJ, Kittler JT (2011). The DISC1Cys607Phe polymorphism affects mitochondrial transport in neurons.. Mol Psychiatry, 16(2), 121 - . doi:10.1038/mp.2010.135
    • Mandal M, Wei J, Zhong P, Cheng J, Duffney LJ, Liu W, Yuen EY, Twelvetrees AE, Li S, Li XJ, Kittler JT, Yan Z (2011). Impaired alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking and function by mutant huntingtin.. J Biol Chem, 286(39), 33719 - 33728. doi:10.1074/jbc.M111.236521
    • Atkin TA, MacAskill AF, Brandon NJ, Kittler JT (2011). Disrupted in Schizophrenia-1 regulates intracellular trafficking of mitochondria in neurons.. Mol Psychiatry, 16(2), 122 - 121. doi:10.1038/mp.2010.110

    2010

    • Burzomato V, Frugier G, Pérez-Otaño I, Kittler JT, Attwell D (2010). The receptor subunits generating NMDA receptor mediated currents in oligodendrocytes.. J Physiol, 588(Pt 18), 3403 - 3414. doi:10.1113/jphysiol.2010.195503
    • Smith KR, Kittler JT (2010). The cell biology of synaptic inhibition in health and disease. Curr Opin Neurobiol, 20(5), 550 - 556. doi:10.1016/j.conb.2010.06.001
    • Twelvetrees AE, Yuen EY, Arancibia-Carcamo IL, MacAskill AF, Rostaing P, Lumb MJ, Humbert S, Triller A, Saudou F, Yan Z, Kittler JT (2010). Delivery of GABAARs to Synapses Is Mediated by HAP1-KIF5 and Disrupted by Mutant Huntingtin. Neuron, 65, 53 - 65.
    • Muir J, Arancibia-Carcamo IL, MacAskill AF, Smith KR, Griffin LD, Kittler JT (2010). NMDA receptors regulate GABAA receptor lateral mobility and clustering at inhibitory synapses through serine 327 on the γ2 subunit.. Proc Natl Acad Sci U S A, 107(38), 16679 - 16684. doi:10.1073/pnas.1000589107
    • MacAskill AF, Atkin TA, Kittler JT (2010). Mitochondrial trafficking and the provision of energy and calcium buffering at excitatory synapses. EUR J NEUROSCI, 32(2), 231 - 240. doi:10.1111/j.1460-9568.2010.07345.x
    • MacAskill AF, Kittler JT (2010). Control of mitochondrial transport and localization in neurons.. Trends Cell Biol, 20(2), 102 - 112. doi:10.1016/j.tcb.2009.11.002
    • Smith KR, Oliver PL, Lumb MJ, Arancibia-Carcamo IL, Revilla-Sanchez R, Brandon NJ, Moss SJ, Kittler JT (2010). Identification and characterisation of a Maf1/Macoco protein complex that interacts with GABAA receptors in neurons.. Mol Cell Neurosci, 44(4), 330 - 341. doi:10.1016/j.mcn.2010.04.004

    2009

    • MacAskill AF, Brickley K, Stephenson FA, Kittler JT (2009). GTPase dependent recruitment of Grif-1 by Miro1 regulates mitochondrial trafficking in hippocampal neurons.. Mol Cell Neurosci, 40(3), 301 - 312. doi:10.1016/j.mcn.2008.10.016
    • Arancibia-Carcamo IL, Yuen EY, Muir J, Lumb MJ, Michels G, Saliba RS, Smart TG, Yan Z, Kittler JT, Moss SJ (2009). Ubiquitin-dependent lysosomal targeting of GABA(A) receptors regulates neuronal inhibition. Proceedings of the National Academy of Sciences of the United States of America, 106(41), 17552 - 17557. doi:10.1073/pnas.0905502106
    • Arancibia-Cárcamo IL, Kittler JT (2009). Regulation of GABA(A) receptor membrane trafficking and synaptic localization.. Pharmacol Ther, 123(1), 17 - 31. doi:10.1016/j.pharmthera.2009.03.012
    • MacAskill AF, Rinholm JE, Twelvetrees AE, Arancibia-Carcamo IL, Muir J, Fransson A, Aspenstrom P, Attwell D, Kittler JT (2009). Miro1 Is a Calcium Sensor for Glutamate Receptor-Dependent Localization of Mitochondria at Synapses. Neuron, 61(4), 541 - 555. doi:10.1016/j.neuron.2009.01.030

    2008

    • Kittler JT, Chen G, Kukhtina V, Vahedi-Faridi A, Gu Z, Tretter V, Smith KR, McAinsh K, Arancibia-Carcamo IL, Saenger W, Haucke V, Yan Z, Moss SJ (2008). Regulation of synaptic inhibition by phospho-dependent binding of the AP2 complex to a YECL motif in the GABAA receptor gamma2 subunit.. Proceedings of the National Academy of Sciences of the United States of America, 105, 3616 - 3621.
    • Arancibia-Carcamo IL, Triller A, Kittler JT (2008). Molecular organisation of the postsynaptic membrane at inhibitory synapses. In: Structural and Functional Organization of the Synapse. In Hell J, Ehlers M (Ed.), Structural and Functional Organization of the Synapse (pp. 621 - 660). : Springer.
    • Terenuma M, Xu J, Vithlani M, Sieghart W, Kittler J, Pangalos M, Haydon PG, Coulter DA, Moss SJ (2008). Deficits in phosphorylation of GABAA receptors by intimately associated protein kinase C activity underlie compromised synaptic inhibition during status epilepticus. Journal of Neuroscience, 28, 376 - 384. doi:10.1523/JNEUROSCI.4346-07.2008
    • Smith KR, McAinsh K, Chen G, Arancibia-Carcamo IL, Haucke V, Yan Z, Moss SJ, Kittler JT (2008). Regulation of inhibitory synaptic transmission by a conserved atypical interaction of GABAA receptor β and γ- subunits with the clathrin AP2 adaptor. Neuropharmacology, 55, 844 - 850. doi:10.1016/j.neuropharm.2008.06.072

    2007

    • Kanematsu T, Fujii M, Mizokami A, Kittler JT, Nabekura J, Moss SJ, Hirata M (2007). Phospholipase C-related inactive protein is implicated in the constitutive internalization of GABAA receptors mediated by clathrin and AP2 adaptor complex. Journal of Neurochemistry, 101, 898 - 905. doi:10.1111/j.1471-4159.2006.04399.x
    • Kastning K, Kukhtina V, Kittler JT, Chen G, Pechstein A, Enders S, Lee SH, Sheng M, Yan Z, Haucke V (2007). Molecular determinants for the interaction between AMPA receptors and the clathrin adaptor complex AP-2. P NATL ACAD SCI USA, 104(8), 2991 - 2996. doi:10.1073/pnas.0611170104

    2006

    • Kanematsu T, Yasunaga A, Mizoguchi Y, Kuratani A, Kittler JT, Jovanovic JN, Takenaka K, Nakayama KI, Fukami K, Takenawa T, Moss SJ, Nabekura J, Hirata M (2006). Modulation of GABAA Receptor Phosphorylation and membrane trafficking by phospholipase C-related inactive protein/protein phosphatase 1 and 2A signaling complex underlying BDNF-dependent regulation of GABAergic inhibition.. Journal of Biological Chemistry, 281(31), 221080 - 221089. doi:10.1074/jbc.M603118200
    • Arancibia-Carcamo L, Fairfax BP, Moss SJ, Kittler JT (2006). Studying the subcellular localisation, surface stability and endocytosis of ionotropic receptors by antibody labelling and biotinylation approaches. In Kittler JT, Moss SJ (Ed.), The dynamic synapse : molecular methods in ionotropic receptor biology (pp. 91 - 118). : CRC/Taylor & Francis, 2006..
    • Kittler JT (2006). The dynamic synapse : molecular methods in ionotropic receptor biology.
    • Kittler JT, Hanley JG, Isaac JTR (2006). Methods for transfecting and transducing neurons. In Kittler JT, Moss SJ (Ed.), The dynamic synapse : molecular methods in ionotropic receptor biology (pp. 205 - 239). : CRC/Taylor & Francis, 2006.
    • Kittler JT (2006). Censoring the editor in transient forebrain ischemia.. Neuron, 49(5), 646 - 648. doi:10.1016/j.neuron.2006.02.013
    • Kittler JT, Oliver P (2006). Genomic and post-genomic tools for studying synapse biology. In Kittler JT, Moss SJ (Ed.), The dynamic synapse : molecular methods in ionotropic receptor biology (pp. 279 - 306). : CRC/Taylor & Francis, 2006.
    • Chen G, Kittler JTJ, Moss SJ, Yan Z (2006). Dopamine D3 receptors regulate GABAA receptor function through a phospho-dependent endocytosis mechanism in nucleus accumbens. Journal of Neuroscience, 26(9), 2513 - 2521. doi:10.1523/JNEUROSCI.4712-05.2006

    2005

    • Jacob TC, Bogdanov YD, Magnus C, Saliba RS, Kittler JT, Haydon PG, Moss SJ (2005). Gephyrin regulates the cell surface dynamics of synaptic GABAA receptors. Journal of Neuroscience, 25(45), 10469 - 10478.
    • Kittler JT, Chen GC, Honing S, Bogdanov Y, McAinsh K, Arancibia-Carcamo L, Jovanovic JN, Pangalos MN, Haucke V, Yan Z, Moss SJ (2005). Phospho-dependent binding of the clathrin AP2 adaptor complex to GABAA receptors regulates the efficacy of inhibitory synaptic transmission. Proceedings of the National Academy of Sciences, 102(41), 14871 - 14876. doi:10.1073/pnas.0506653102

    2004

    • Kittler JT, Arancibia-Carcamo IL, Moss SJ (2004). Association of GRIP1 with a GABA(A) receptor associated protein suggests a role for GRIP1 at inhibitory synapses.. Biochemical Pharmacology, 68, 1649 - 1654.
    • Rathenberg J, Kittler JT, Moss SJ (2004). Palmitoylation regulates the clustering and cell surface stability of GABAA receptors.. Molecular and Cellular Neuroscience, 26(2), 251 - 257.
    • Terunuma M, Jang IS, Ha SH, Kittler JT, Kanematsu T, Jovanovic JN, Nakayama KI, Akaike N, Ryu SH, Moss SJ, Hirata M (2004). GABA(A) receptor phospho-dependent modulation is regulated by phospholipase C-related inactive protein type 1, a novel protein phosphatase 1 anchoring protein. J NEUROSCI, 24(32), 7074 - 7084. doi:10.1523/JNEUROSCI.1323-04.2004
    • Kittler JT, Thomas P, Tretter V, Bogdanov YD, Haucke V, Smart TG, Moss SJ (2004). Huntingtin-associated protein 1 regulates inhibitory synaptic transmission by modulating gamma-aminobutyric acid type A receptor membrane trafficking. Proceedings of the National Academy of Sciences of the United States of America, 101(34), 12736 - 12741. doi:10.1073/pnas.0401860101
    • Jovanovic JN, Thomas P, Kittler JT, Smart TG, Moss SJ (2004). BDNF modulates fast synaptic inhibition by regulating GABAA receptor phosphorylation, activity and cell surface stability.. Journal of Neuroscience, 24(2), 522 - 530. doi:10.1523/JNEUROSCI.3606-03.2004

    2003

    • Marie H, Pratt SJ, Betson M, Epple H, Kittler JT, Meek L, Moss SJ, Troyanovsky S, Attwell D, Longmore GD, Braga VM (2003). The LIM protein Ajuba is recruited to cadherin-dependent cell junctions through an association with alpha-catenin. Journal of Biological Chemistry, 278, 1220 - 1228.
    • Brandon NJ, Jovanovic JN, Colledge M, Kittler JT, Brandon JM, Scott JD, Moss SJ (2003). A-kinase anchoring protein 79/150 facilitates the phosphorylation of GABAA receptors by cAMP-dependent protein kinase via selective interaction with receptor ? subunits. Molecular and Cellular Neuroscience, 22(1), 87 - 97. doi:10.1016/S1044-7431(02)00017-9
    • Kittler JT, Moss SJ (2003). Modulation of GABAA receptor activity by phosphorylation and receptor trafficking: implications for the efficacy of synaptic inhibition. Current Opinion in Neurobiology, 13, 341 - 347. doi:10.1016/S0959-4388(03)00064-3

    2002

    • Nymann-Andersen J, Wang H, Chen L, Kittler JT, Moss SJ, Olsen RW (2002). Subunit specificity and interaction domain between GABA(A) receptor-associated protein (GABARAP) and GABA(A) receptors.. Journal of Neurochemistry, 80(5), 815 - 823.
    • Kittler J, Zhuang S-Y CC, Wallace D DSA, Grigorenko EV (2002). Application of Arrayed Libraries for Analysis of Differential Gene Expression Following Chronic Cannabinoid Exposure. In Grigorenko EV (Ed.), DNA Arrays: Technologies and Experimental Strategies (pp. 141 - 155). : CRC Press.
    • Kittler JT, McAinsh K, Moss SJ (2002). Mechanisms of GABAA receptor assembly and trafficking: implications for the modulation of inhibitory neurotransmission. Molecular Neurobiology, 26, 251 - 268. doi:10.1385/MN:26:2-3:251
    • Grigorenko E, Kittler J, Clayton C, Wallace D, Zhuang S, Bridges D, Bundey S, Boon A, Pagget C, Hayashizaki S, Lowe G, Hampson R, Deadwyler S (2002). Assessment of cannabinoid induced gene changes: tolerance and neuroprotection.. Chemistry and Physics of Lipids, 121(1-2), 257 - 266. doi:10.1016/S0009-3084(02)00161-5

    2001

    • Bedford FK, Kittler JT, Muller E, Thomas P, Uren JM, Merlo D, Wisden W, Triller A, Smart TG, Moss SJ (2001). GABAA receptor cell surface number and subunit stability are regulated by the ubiquitin like protein Plic-1. Nature Neuroscience, 4, 917 - 926. doi:10.1038/nn0901-908
    • Kittler JT, Moss SJ (2001). Neurotransmitter receptor trafficking and the regulation of synaptic strength. Traffic, 2, 437 - 448. doi:10.1034/j.1600-0854.2001.20702.x
    • Couve A, Kittler JT, Uren JM, Calver AR, Pangalos MN, Walsh FS, Moss SJ (2001). Association of GABA(B) receptors and members of the 14-3-3 family of signaling proteins. MOL CELL NEUROSCI, 17(2), 317 - 328. doi:10.1006/mcn3.2000.0938
    • Kittler JT, Rostaing P, Schiavo G, Fritschy JM, Olsen R, Triller A, Moss SJ (2001). The subcellular distribution of GABARAP and its ability to interact with NSF suggest a role for this protein in the intracellular transport of GABAA receptors. Molecular and Cellular Neuroscience, 18, 13 - 25. doi:10.1006/mcne.2001.1005

    2000

    • Kittler JT, Grigorenko EV, Clayton C, Zhuang SY, Bundey SC, Trower MM, Wallace D, Hampson R, Deadwyler S (2000). Large-scale analysis of gene expression changes during acute and chronic exposure to Delta(9)-THC in rats. PHYSIOL GENOMICS, 3(3), 175 - 185.
    • Brandon N, Delmas P, Kittler JT, McDonald BJ, Sieghart W, Brown DA, Smart TG, Moss SJ (2000). GABAA receptor phosphorylation and functional modulation in cortical neurons by a protein kinase C-dependent pathway. Journal of Biological Chemistry, 275, 38856 - 38862.
    • Kittler JT, Wang J, Connolly CN, Vicini S, Smart TG, Moss SJ (2000). Analysis of GABAA receptor assembly in mammalian cell lines and hippocampal neurons using 2 subunit green fluorescent protein chimeras. Molecular and Cellular Neuroscience, 16, 440 - 452.
    • Kittler JT, Delmas P, Jovanovic JN, Brown DA, Smart TG, Moss SJ (2000). Constitutive endocytosis of GABA(A) receptors by an association with the adaptin AP2 complex modulates inhibitory synaptic currents in hippocampal neurons. Journal of Neuroscience, 20(21), 7972 - 7977.
    • Taylor PM, Connolly CN, Kittler JT, Gorrie GH, Hosie A, Smart TG, Moss SJ (2000). Identification of residues within GABA(A) receptor alpha subunits that mediate specific assembly with receptor beta subunits. J NEUROSCI, 20(4), 1297 - 1306.
    • Cockcroft S (2000). Preface. In Cockcroft S (Ed.), Biology of Phosphoinositides (pp. - ). : Oxford University Press.

    1999

    • Brandon NJ, Uren JM, Kittler JT, Wang H, Olsen R, Parker PJ, Moss SJ (1999). Subunit-specific association of protein kinase C and the receptor for activated C kinase with GABA type A receptors. Journal of Neuroscience, 19(21), 9228 - 9234.
    • Brandon NJ, Bedford FK, Connolly CN, Couve A, Kittler JT, Hanley JG, Jovanovic JN, Uren J, Taylor PW, Thomas P, Smart TG, Moss SJ (1999). Synaptic targeting and regulation of GABA(A) receptors. doi:10.1042/bst0270527
    • Bedford FK, Brandon NJ, Connolly CN, Kittler JT, Hanley JG, Jovanovic J, Uren J, Moss SJ (1999). Mechanisms underlying the subcellular localisation of ionotropic GABA receptors. J NEUROCHEM, 73, S165 - S165.
    • Connolly CN, Kittler JT, Thomas P, Uren JM, Brandon NJ, Smart TG, Moss SJ (1999). Cell surface stability of gamma-aminobutyric acid type A receptors. Dependence on protein kinase C activity and subunit composition.. J Biol Chem, 274(51), 36565 - 36572.

    1998

    • Zhuang S, Kittler J, Grigorenko EV, Kirby MT, Sim LJ, Hampson RE, Childers SR, Deadwyler SA (1998). Effects of long-term exposure to delta9-THC on expression of cannabinoid receptor (CB1) mRNA in different rat brain regions.. Molecular Brain Research, 62, 141 - 149. doi:10.1016/S0169-328X(98)00232-0

    1986