Dr Tony Jackson

Tony Jackson

University position

Senior Lecturer

Dr Tony Jackson is pleased to consider applications from prospective PhD students.

Departments

Department of Biochemistry

Institutes

Cambridge Crystallographic Data Centre

Email

apj10@cam.ac.uk

Home page

http://www.bioc.cam.ac.uk/

Research Theme

Cellular and Molecular Neuroscience

Interests

In neurones, voltage-gated sodium (Nav) channels initiate the action potential. Sodium channels consist of a ~ 250 kDa alpha-subunit and ~40 kDa beta-subunits. The beta-subunits modulate channel gating. The Nav beta-subunits possess an extracellular immunoglobulin (Ig) domain, connected to an alpha-helical transmembrane domain and an intracellular carboxy-terminal region.

We study the structure and function of the Nav channel beta 3-subunit. We determined the structure of the beta 3-subunit Ig domain using X-ray crystallography. We have shown that the beta3-subunits trimerise via their Ig domains, and cross-link Nav channel alpha-subunits.

These results provide a new interpretation of previous electrophysiological data, and raise new questions. Does Nav channel cross-linking by beta 3 lead to functionally coupled channels? Can different Nav alpha-subunit isoforms be cross-linked together? Do beta-subunits stabilise Nav channels into larger protein clusters on the plasma membrane?

The predicted structure of the beta 3 extracellular domain
The structure of the Nav channel beta 3 subunit immunoglobulin (Ig) domain
Click image to view full-size

Research Focus

Keywords

sodium channels

membrane traffic

cell biology

proteomic methods

Clinical conditions

Alzheimer's disease

Autoimmune diseases

Cancers

Epilepsy

Genetic disorders

Equipment

Cell culture

Confocal microscopy

Electrophysiological recording techniques

Enzyme assays

Protein purification

Proteomic methods for studying localised protein clusters on the plasma membrane.

Whole cell patch clamp

X-ray crystallography

Collaborators

Cambridge

Dimitry Chirgadze

J Michael Edwardson

Andrew Grace

Chris Huang

Kathryn Lilley

International

Manoj Patel Web: http://www.healthsystem.virginia.edu/interne...

Sarah Perrett Web: http://sourcedb.cas.cn/sourced...

Revaz Solomonia Web: http://www.acnet.ge/

Associated News Items


    Key publications

    Namadurai S, Balasuriya D, Rajappa R, Wiemhöfer M, Stott K, Klingauf J, Edwardson JM, Chirgadze DY, Jackson AP (2014), “Crystal structure and molecular imaging of the Nav channel β3 subunit indicates a trimeric assembly.” J Biol Chem 289(15):10797-811 Details

    Hakim P, Brice N, Thresher R, Lawrence J, Zhang Y, Jackson AP, Grace AA, Huang CL (2010), “Scn3b knockout mice exhibit abnormal sino-atrial and cardiac conduction properties.” Acta Physiol (Oxf) 198(1):47-59 Details

    Yu EJ, Ko SH, Lenkowski PW, Pance A, Patel MK, Jackson AP (2005), “Distinct domains of the sodium channel beta3-subunit modulate channel-gating kinetics and subcellular location.” Biochem J 392(Pt 3):519-26 Details

    Morgan K, Stevens EB, Shah B, Cox PJ, Dixon AK, Lee K, Pinnock RD, Hughes J, Richardson PJ, Mizuguchi K, Jackson AP (2000), “beta 3: an additional auxiliary subunit of the voltage-sensitive sodium channel that modulates channel gating with distinct kinetics.” Proc Natl Acad Sci U S A 97(5):2308-13 Details

    Publications

    2014

    Li XW, Rees JS, Xue P, Zhang H, Hamaia SW, Sanderson B, Funk PE, Farndale RW, Lilley KS, Perrett S, Jackson AP (2014), “New Insights into the DT40 B-Cell Receptor Cluster using a Proteomic Proximity Labeling Assay.” J Biol Chem Details

    2013

    Yereddi NR, Cusdin FS, Namadurai S, Packman LC, Monie TP, Slavny P, Clare JJ, Powell AJ, Jackson AP (2013), “The immunoglobulin domain of the sodium channel β3 subunit contains a surface-localized disulfide bond that is required for homophilic binding.” FASEB J 27(2):568-80 Details

    2010

    Cusdin FS, Nietlispach D, Maman J, Dale TJ, Powell AJ, Clare JJ, Jackson AP (2010), “The sodium channel {beta}3-subunit induces multiphasic gating in NaV1.3 and affects fast inactivation via distinct intracellular regions.” J Biol Chem 285(43):33404-12 Details

    Merrick EC, Kalmar CL, Snyder SL, Cusdin FS, Yu EJ, Sando JJ, Isakson BE, Jackson AP, Patel MK (2010), “The importance of serine 161 in the sodium channel beta3 subunit for modulation of Na(V)1.2 gating.” Pflugers Arch 460(4):743-53 Details

    Neumann-Staubitz P, Hall SL, Kuo J, Jackson AP (2010), “Characterization of a temperature-sensitive vertebrate clathrin heavy chain mutant as a tool to study clathrin-dependent events in vivo.” PLoS One 5(8) Details

    Zhang C, Jackson AP, Zhang ZR, Han Y, Yu S, He RQ, Perrett S (2010), “Amyloid-like aggregates of the yeast prion protein ure2 enter vertebrate cells by specific endocytotic pathways and induce apoptosis.” PLoS One 5(9) Details

    2009

    Hall SL, Hester S, Griffin JL, Lilley KS, Jackson AP (2009), “The organelle proteome of the DT40 lymphocyte cell line.” Mol Cell Proteomics 8(6):1295-305 Details

    van Gassen KL, de Wit M, van Kempen M, van der Hel WS, van Rijen PC, Jackson AP, Lindhout D, de Graan PN (2009), “Hippocampal Nabeta3 expression in patients with temporal lobe epilepsy.” Epilepsia 50(4):957-62 Details

    2008

    Borlido J, Veltri G, Jackson AP, Mills IG (2008), “Clathrin is spindle-associated but not essential for mitosis.” PLoS One 3(9):e3115 Details

    Cusdin FS, Clare JJ, Jackson AP (2008), “Trafficking and cellular distribution of voltage-gated sodium channels.” Traffic 9(1):17-26 Details

    Solomonia RO, Apkhazava D, Nozadze M, Jackson AP, McCabe BJ, Horn G (2008), “Different forms of MARCKS protein are involved in memory formation in the learning process of imprinting.” Exp Brain Res 188(2):323-30 Details

    2006

    Courel M, Rodemer C, Nguyen ST, Pance A, Jackson AP, O'connor DT, Taupenot L (2006), “Secretory granule biogenesis in sympathoadrenal cells: identification of a granulogenic determinant in the secretory prohormone chromogranin A.” J Biol Chem 281(49):38038-51 Details

    Pance A, Livesey FJ, Jackson AP (2006), “A role for the transcriptional repressor REST in maintaining the phenotype of neurosecretory-deficient PC12 cells.” J Neurochem 99(5):1435-44 Details

    Wettey FR, Jackson AP (2006), “Using DT40 to study clathrin function.” Subcell Biochem 40:119-43 Details

    2005

    Bentrari F, Arnould L, Jackson AP, Jeannin JF, Pance A (2005), “Progesterone enhances cytokine-stimulated nitric oxide synthase II expression and cell death in human breast cancer cells.” Lab Invest 85(5):624-32 Details

    Diaz-Griffero F, Jackson AP, Brojatsch J (2005), “Cellular uptake of avian leukosis virus subgroup B is mediated by clathrin.” Virology 337(1):45-54 Details

    Flett A, Semerdjieva S, Jackson AP, Smythe E (2005), “Regulation of the clathrin-coated vesicle cycle by reversible phosphorylation.” Biochem Soc Symp (72):65-70 Details

    Stoddart A, Jackson AP, Brodsky FM (2005), “Plasticity of B cell receptor internalization upon conditional depletion of clathrin.” Mol Biol Cell 16(5):2339-48 Details

    2003

    Jackson AP, Flett A, Smythe C, Hufton L, Wettey FR, Smythe E (2003), “Clathrin promotes incorporation of cargo into coated pits by activation of the AP2 adaptor micro2 kinase.” J Cell Biol 163(2):231-6 Details

    Solomonia RO, Morgan K, Kotorashvili A, McCabe BJ, Jackson AP, Horn G (2003), “Analysis of differential gene expression supports a role for amyloid precursor protein and a protein kinase C substrate (MARCKS) in long-term memory.” Eur J Neurosci 17(5):1073-81 Details

    2002

    Wettey FR, Hawkins SF, Stewart A, Luzio JP, Howard JC, Jackson AP (2002), “Controlled elimination of clathrin heavy-chain expression in DT40 lymphocytes.” Science 297(5586):1521-5 Details

    2001

    Fahmi AI, Patel M, Stevens EB, Fowden AL, John JE 3rd, Lee K, Pinnock R, Morgan K, Jackson AP, Vandenberg JI (2001), “The sodium channel beta-subunit SCN3b modulates the kinetics of SCN5a and is expressed heterogeneously in sheep heart.” J Physiol 537(Pt 3):693-700 Details

    Razzaq A, Robinson IM, McMahon HT, Skepper JN, Su Y, Zelhof AC, Jackson AP, Gay NJ, O'Kane CJ (2001), “Amphiphysin is necessary for organization of the excitation-contraction coupling machinery of muscles, but not for synaptic vesicle endocytosis in Drosophila.” Genes Dev 15(22):2967-79 Details

    2000

    Razzaq A, Su Y, Mehren JE, Mizuguchi K, Jackson AP, Gay NJ, O'Kane CJ (2000), “Characterisation of the gene for Drosophila amphiphysin.” Gene 241(1):167-74 Details

    1999

    Pance A, Morgan K, Guest PC, Bowers K, Dean GE, Cutler DF, Jackson AP (1999), “A PC12 variant lacking regulated secretory organelles: aberrant protein targeting and evidence for a factor inhibiting neuroendocrine gene expression.” J Neurochem 73(1):21-30 Details

    1997

    Dornan S, Jackson AP, Gay NJ (1997), “Alpha-adaptin, a marker for endocytosis, is expressed in complex patterns during Drosophila development.” Mol Biol Cell 8(8):1391-403 Details

    Solomonia RO, McCabe BJ, Jackson AP, Horn G (1997), “Clathrin proteins and recognition memory.” Neuroscience 80(1):59-67 Details

    1996

    Cheetham ME, Anderton BH, Jackson AP (1996), “Inhibition of hsc70-catalysed clathrin uncoating by HSJ1 proteins.” Biochem J 319 ( Pt 1):103-8 Details

    1994

    Cheetham ME, Jackson AP, Anderton BH (1994), “Regulation of 70-kDa heat-shock-protein ATPase activity and substrate binding by human DnaJ-like proteins, HSJ1a and HSJ1b.” Eur J Biochem 226(1):99-107 Details