Dr Tony Jackson University positionSenior Lecturer Dr Tony Jackson is pleased to consider applications from prospective PhD students. DepartmentsInstitutesCambridge Crystallographic Data Centre Home pageResearch ThemeInterestsIn 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 structure of the Nav channel beta 3 subunit immunoglobulin (Ig) domain Click image to view full-size Research Focus
EquipmentCell 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
Associated News ItemsKey publicationsNamadurai 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 ?3 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 Publications2014Li 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 2013Yereddi 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 ?3 subunit contains a surface-localized disulfide bond that is required for homophilic binding.” FASEB J 27(2):568-80 Details 2010Cusdin 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 2009Hall 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 2008Borlido 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 2006Courel 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 2005Bentrari 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 2003Jackson 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 2002Wettey 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 2001Fahmi 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 2000Razzaq 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 1999Pance 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 1997Dornan 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 1996Cheetham ME, Anderton BH, Jackson AP (1996), “Inhibition of hsc70-catalysed clathrin uncoating by HSJ1 proteins.” Biochem J 319 ( Pt 1):103-8 Details 1994Cheetham 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 |