William Green

Research Summary
My research is focused on ionotropic neurotransmitter receptors, the receptors responsible for the rapid postsynaptic response in nerve and muscle. These receptors are large oligomeric membrane proteins with subunits surrounding an ion channel that opens when neurotransmitters bind to the receptor. There are two different families of ionotropic neurotransmitter receptors. One family includes nicotinic acetylcholine receptors (AChRs), GABA and glycine receptors, and the other family are glutamate receptors, both NMDA- and AMPA-type glutamate receptors. The overall goal of my research is to understand how nerve and muscle build these receptors and traffic them specifically to and from synapses. These events regulate the number, density and function of the receptors at synapses, which helps define synaptic strength. The same events underlie learning and memory formation, and when they fail, can contribute to a number of diseases including Alzheimer’s disease, Huntington’s Disease, Myasthenia Gravis and Myasthenic Syndromes. There are several projects ongoing in my lab characterizing the basic cell biology of these receptors, which include receptor assembly, trafficking and clustering. Assembly refers to the processes that transform newly synthesized subunits into functional receptors usually in the endoplasmic reticulum. Trafficking refers to the processes that transport the receptors to and from different location in cells and targets them to these locations. Clustering is the process that packs and maintains the receptors in regions of high density such as synapses. Recently, we have developed new techniques for assaying the protein post-translation modification known as palmitoylation. This work has led to several collaborations in which we are helping to characterize the palmitoylation of a number of different proteins. I also am collaborating with Dr. Paul Selvin (University of Illinois) developing fluorescent single-molecule methods to characterize neurotransmitter receptor subunit composition, stoichiometry and the diffusion/trafficking of these receptors.
Keywords
Acetylcholine, Acetylcholine Receptors, Nicotinic, Glutamate, Glutamate Receptors, Ionotropic, Synapses, Trafficking, Protein, Cell Biology of Neurons, Nicotine, Nicotine Addiction
Education
  • Yale University, New Haven, CT, Postdoctoral Fellow Physiology & Neuroscience 12/1992
  • Cornell University Graduate School of Medical Sciences, New York, NY, Ph.D. Physiology & Biophysics 06/1986
  • University College, University of Toronto, Toronto, Canada , B.Sc. Physics & Zoology 06/1978
Publications
  1. Samra GK, Intskirveli I, Govind AP, Liang C, Lazar R, Green WN, Metherate R, Mukherjee J. Development of fluorescence imaging probes for nicotinic acetylcholine a4ß2* receptors. Bioorg Med Chem Lett. 2018 02 01; 28(3):371-377. View in: PubMed

  2. Lee SH, Jin C, Cai E, Ge P, Ishitsuka Y, Teng KW, de Thomaz AA, Nall D, Baday M, Jeyifous O, Demonte D, Dundas CM, Park S, Delgado JY, Green WN, Selvin PR. Correction: Super-resolution imaging of synaptic and Extra-synaptic AMPA receptors with different-sized fluorescent probes. Elife. 2017 11 08; 6. View in: PubMed

  3. Lee SH, Jin C, Cai E, Ge P, Ishitsuka Y, Teng KW, de Thomaz AA, Nall D, Baday M, Jeyifous O, Demonte D, Dundas CM, Park S, Delgado JY, Green WN, Selvin PR. Super-resolution imaging of synaptic and Extra-synaptic AMPA receptors with different-sized fluorescent probes. Elife. 2017 07 27; 6. View in: PubMed

  4. Govind AP, Vallejo YF, Stolz JR, Yan JZ, Swanson GT, Green WN. Selective and regulated trapping of nicotinic receptor weak base ligands and relevance to smoking cessation. Elife. 2017 07 18; 6. View in: PubMed

  5. Antinone SE, Ghadge GD, Ostrow LW, Roos RP, Green WN. S-acylation of SOD1, CCS, and a stable SOD1-CCS heterodimer in human spinal cords from ALS and non-ALS subjects. Sci Rep. 2017 01 25; 7:41141. View in: PubMed

  6. Jeyifous O, Lin EI, Chen X, Antinone SE, Mastro R, Drisdel R, Reese TS, Green WN. Palmitoylation regulates glutamate receptor distributions in postsynaptic densities through control of PSD95 conformation and orientation. Proc Natl Acad Sci U S A. 2016 12 27; 113(52):E8482-E8491. View in: PubMed

  7. Zheng N, Jeyifous O, Munro C, Montgomery JM, Green WN. Synaptic activity regulates AMPA receptor trafficking through different recycling pathways. Elife. 2015 May 13; 4. View in: PubMed

  8. Wang Y, Cai E, Rosenkranz T, Ge P, Teng KW, Lim SJ, Smith AM, Chung HJ, Sachs F, Green WN, Gottlieb P, Selvin PR. Small quantum dots conjugated to nanobodies as immunofluorescence probes for nanometric microscopy. Bioconjug Chem. 2014 Dec 17; 25(12):2205-11. View in: PubMed

  9. Cai E, Ge P, Lee SH, Jeyifous O, Wang Y, Liu Y, Wilson KM, Lim SJ, Baird MA, Stone JE, Lee KY, Davidson MW, Chung HJ, Schulten K, Smith AM, Green WN, Selvin PR. Stable small quantum dots for synaptic receptor tracking on live neurons. Angew Chem Int Ed Engl. 2014 Nov 10; 53(46):12484-8. View in: PubMed

  10. Cortes CJ, Qin K, Norstrom EM, Green WN, Bindokas VP, Mastrianni JA. Early Delivery of Misfolded PrP from ER to Lysosomes by Autophagy. Int J Cell Biol. 2013; 2013:560421. View in: PubMed

  11. O'Connor MA, Green WR. Use of IRF-3 and/or IRF-7 knockout mice to study viral pathogenesis: lessons from a murine retrovirus-induced AIDS model. J Virol. 2014 Feb; 88(4):2349-53. View in: PubMed

  12. Lin EI, Jeyifous O, Green WN. CASK regulates SAP97 conformation and its interactions with AMPA and NMDA receptors. J Neurosci. 2013 Jul 17; 33(29):12067-76. View in: PubMed

  13. Antinone SE, Ghadge GD, Lam TT, Wang L, Roos RP, Green WN. Palmitoylation of superoxide dismutase 1 (SOD1) is increased for familial amyotrophic lateral sclerosis-linked SOD1 mutants. J Biol Chem. 2013 Jul 26; 288(30):21606-17. View in: PubMed

  14. Baker LK, Mao D, Chi H, Govind AP, Vallejo YF, Iacoviello M, Herrera S, Cortright JJ, Green WN, McGehee DS, Vezina P. Intermittent nicotine exposure upregulates nAChRs in VTA dopamine neurons and sensitises locomotor responding to the drug. Eur J Neurosci. 2013 Mar; 37(6):1004-11. View in: PubMed

  15. Govind AP, Walsh H, Green WN. Nicotine-induced upregulation of native neuronal nicotinic receptors is caused by multiple mechanisms. J Neurosci. 2012 Feb 08; 32(6):2227-38. View in: PubMed

  16. Singaraja RR, Huang K, Sanders SS, Milnerwood AJ, Hines R, Lerch JP, Franciosi S, Drisdel RC, Vaid K, Young FB, Doty C, Wan J, Bissada N, Henkelman RM, Green WN, Davis NG, Raymond LA, Hayden MR. Altered palmitoylation and neuropathological deficits in mice lacking HIP14. Hum Mol Genet. 2011 Oct 15; 20(20):3899-909. View in: PubMed

  17. Carlson TL, Green KA, Green WR. Alternative translational reading frames as a novel source of epitopes for an expanded CD8 T-cell repertoire: use of a retroviral system to assess the translational requirements for CTL recognition and lysis. Viral Immunol. 2010 Dec; 23(6):577-83. View in: PubMed

  18. Simonson PD, Deberg HA, Ge P, Alexander JK, Jeyifous O, Green WN, Selvin PR. Counting bungarotoxin binding sites of nicotinic acetylcholine receptors in mammalian cells with high signal/noise ratios. Biophys J. 2010 Nov 17; 99(10):L81-3. View in: PubMed

  19. Alexander JK, Sagher D, Krivoshein AV, Criado M, Jefford G, Green WN. Ric-3 promotes alpha7 nicotinic receptor assembly and trafficking through the ER subcompartment of dendrites. J Neurosci. 2010 Jul 28; 30(30):10112-26. View in: PubMed

  20. Alexander JK, Govind AP, Drisdel RC, Blanton MP, Vallejo Y, Lam TT, Green WN. Palmitoylation of nicotinic acetylcholine receptors. J Mol Neurosci. 2010 Jan; 40(1-2):12-20. View in: PubMed

  21. Jeyifous O, Waites CL, Specht CG, Fujisawa S, Schubert M, Lin EI, Marshall J, Aoki C, de Silva T, Montgomery JM, Garner CC, Green WN. SAP97 and CASK mediate sorting of NMDA receptors through a previously unknown secretory pathway. Nat Neurosci. 2009 Aug; 12(8):1011-9. View in: PubMed

  22. Singaraja RR, Kang MH, Vaid K, Sanders SS, Vilas GL, Arstikaitis P, Coutinho J, Drisdel RC, El-Husseini Ael D, Green WN, Berthiaume L, Hayden MR. Palmitoylation of ATP-binding cassette transporter A1 is essential for its trafficking and function. Circ Res. 2009 Jul 17; 105(2):138-47. View in: PubMed

  23. Govind AP, Vezina P, Green WN. Nicotine-induced upregulation of nicotinic receptors: underlying mechanisms and relevance to nicotine addiction. Biochem Pharmacol. 2009 Oct 01; 78(7):756-65. View in: PubMed

  24. Waites CL, Specht CG, Härtel K, Leal-Ortiz S, Genoux D, Li D, Drisdel RC, Jeyifous O, Cheyne JE, Green WN, Montgomery JM, Garner CC. Synaptic SAP97 isoforms regulate AMPA receptor dynamics and access to presynaptic glutamate. J Neurosci. 2009 Apr 08; 29(14):4332-45. View in: PubMed

  25. Kang R, Wan J, Arstikaitis P, Takahashi H, Huang K, Bailey AO, Thompson JX, Roth AF, Drisdel RC, Mastro R, Green WN, Yates JR, Davis NG, El-Husseini A. Neural palmitoyl-proteomics reveals dynamic synaptic palmitoylation. Nature. 2008 Dec 18; 456(7224):904-9. View in: PubMed

  26. Cheng H, Vetrivel KS, Drisdel RC, Meckler X, Gong P, Leem JY, Li T, Carter M, Chen Y, Nguyen P, Iwatsubo T, Tomita T, Wong PC, Green WN, Kounnas MZ, Thinakaran G. S-palmitoylation of gamma-secretase subunits nicastrin and APH-1. J Biol Chem. 2009 Jan 16; 284(3):1373-84. View in: PubMed

  27. Liu Y, Padgett D, Takahashi M, Li H, Sayeed A, Teichert RW, Olivera BM, McArdle JJ, Green WN, Lin W. Essential roles of the acetylcholine receptor gamma-subunit in neuromuscular synaptic patterning. Development. 2008 Jun; 135(11):1957-67. View in: PubMed

  28. Walsh H, Govind AP, Mastro R, Hoda JC, Bertrand D, Vallejo Y, Green WN. Up-regulation of nicotinic receptors by nicotine varies with receptor subtype. J Biol Chem. 2008 Mar 07; 283(10):6022-32. View in: PubMed

  29. Vezina P, McGehee DS, Green WN. Exposure to nicotine and sensitization of nicotine-induced behaviors. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Nov 15; 31(8):1625-38. View in: PubMed

  30. Wanamaker CP, Green WN. Endoplasmic reticulum chaperones stabilize nicotinic receptor subunits and regulate receptor assembly. J Biol Chem. 2007 Oct 26; 282(43):31113-23. View in: PubMed

  31. Drisdel RC, Sharp D, Henderson T, Hales TG, Green WN. High affinity binding of epibatidine to serotonin type 3 receptors. J Biol Chem. 2008 Apr 11; 283(15):9659-65. View in: PubMed

  32. Roth AF, Wan J, Green WN, Yates JR, Davis NG. Proteomic identification of palmitoylated proteins. Methods. 2006 Oct; 40(2):135-42. View in: PubMed

  33. Drisdel RC, Alexander JK, Sayeed A, Green WN. Assays of protein palmitoylation. Methods. 2006 Oct; 40(2):127-34. View in: PubMed

  34. Roth AF, Wan J, Bailey AO, Sun B, Kuchar JA, Green WN, Phinney BS, Yates JR, Davis NG. Global analysis of protein palmitoylation in yeast. Cell. 2006 Jun 02; 125(5):1003-13. View in: PubMed

  35. Yanai A, Huang K, Kang R, Singaraja RR, Arstikaitis P, Gan L, Orban PC, Mullard A, Cowan CM, Raymond LA, Drisdel RC, Green WN, Ravikumar B, Rubinsztein DC, El-Husseini A, Hayden MR. Palmitoylation of huntingtin by HIP14 is essential for its trafficking and function. Nat Neurosci. 2006 Jun; 9(6):824-31. View in: PubMed

  36. Wanamaker CP, Green WN. N-linked glycosylation is required for nicotinic receptor assembly but not for subunit associations with calnexin. J Biol Chem. 2005 Oct 07; 280(40):33800-10. View in: PubMed

  37. Vallejo YF, Buisson B, Bertrand D, Green WN. Chronic nicotine exposure upregulates nicotinic receptors by a novel mechanism. J Neurosci. 2005 Jun 08; 25(23):5563-72. View in: PubMed

  38. Drisdel RC, Manzana E, Green WN. The role of palmitoylation in functional expression of nicotinic alpha7 receptors. J Neurosci. 2004 Nov 17; 24(46):10502-10. View in: PubMed

  39. Christianson JC, Green WN. Regulation of nicotinic receptor expression by the ubiquitin-proteasome system. EMBO J. 2004 Oct 27; 23(21):4156-65. View in: PubMed

  40. Drisdel RC, Green WN. Labeling and quantifying sites of protein palmitoylation. Biotechniques. 2004 Feb; 36(2):276-85. View in: PubMed

  41. Wanamaker CP, Christianson JC, Green WN. Regulation of nicotinic acetylcholine receptor assembly. Ann N Y Acad Sci. 2003 Sep; 998:66-80. View in: PubMed

  42. Kopito RR, Green WN, Andersen O. The 56th Annual Meeting and Symposium of the Society of General Physiologists: trafficking of transporters. J Gen Physiol. 2003 Feb; 121(2):73-9. View in: PubMed

  43. Leem JY, Saura CA, Pietrzik C, Christianson J, Wanamaker C, King LT, Veselits ML, Tomita T, Gasparini L, Iwatsubo T, Xu H, Green WN, Koo EH, Thinakaran G. A role for presenilin 1 in regulating the delivery of amyloid precursor protein to the cell surface. Neurobiol Dis. 2002 Oct; 11(1):64-82. View in: PubMed

  44. Ghazi NG, Green WR. Pathology and pathogenesis of retinal detachment. Eye (Lond). 2002 Jul; 16(4):411-21. View in: PubMed

  45. Mitra M, Wanamaker CP, Green WN. Rearrangement of nicotinic receptor alpha subunits during formation of the ligand binding sites. J Neurosci. 2001 May 01; 21(9):3000-8. View in: PubMed

  46. Knox DL, Kerrison JB, Green WR. Histopathologic studies of ischemic optic neuropathy. Trans Am Ophthalmol Soc. 2000; 98:203-20; discussion 221-2. View in: PubMed

  47. Buisson B, Vallejo YF, Green WN, Bertrand D. The unusual nature of epibatidine responses at the alpha4beta2 nicotinic acetylcholine receptor. Neuropharmacology. 2000 Oct; 39(13):2561-9. View in: PubMed

  48. Hayashi N, Geraghty MT, Green WR. Ocular histopathologic study of a patient with the T 8993-G point mutation in Leigh's syndrome. Ophthalmology. 2000 Jul; 107(7):1397-402. View in: PubMed

  49. Drisdel RC, Green WN. Neuronal alpha-bungarotoxin receptors are alpha7 subunit homomers. J Neurosci. 2000 Jan 01; 20(1):133-9. View in: PubMed

  50. Eertmoed AL, Green WN. Nicotinic receptor assembly requires multiple regions throughout the gamma subunit. J Neurosci. 1999 Aug 01; 19(15):6298-308. View in: PubMed

  51. Rakhilin S, Drisdel RC, Sagher D, McGehee DS, Vallejo Y, Green WN. alpha-bungarotoxin receptors contain alpha7 subunits in two different disulfide-bonded conformations. J Cell Biol. 1999 Jul 12; 146(1):203-18. View in: PubMed

  52. Green WN. Ion channel assembly: creating structures that function. J Gen Physiol. 1999 Feb; 113(2):163-70. View in: PubMed

  53. Eertmoed AL, Vallejo YF, Green WN. Transient expression of heteromeric ion channels. Methods Enzymol. 1998; 293:564-85. View in: PubMed

  54. Green WN, Wanamaker CP. Formation of the nicotinic acetylcholine receptor binding sites. J Neurosci. 1998 Aug 01; 18(15):5555-64. View in: PubMed

  55. Mayrand SM, Schwarz DA, Green WR. An alternative translational reading frame encodes an immunodominant retroviral CTL determinant expressed by an immunodeficiency-causing retrovirus. J Immunol. 1998 Jan 01; 160(1):39-50. View in: PubMed

  56. Green KA, Noelle RJ, Green WR. Evidence for a continued requirement for CD40/CD40 ligand (CD154) interactions in the progression of LP-BM5 retrovirus-induced murine AIDS. Virology. 1998 Feb 15; 241(2):260-8. View in: PubMed

  57. Rangwala F, Drisdel RC, Rakhilin S, Ko E, Atluri P, Harkins AB, Fox AP, Salman SS, Green WN. Neuronal alpha-bungarotoxin receptors differ structurally from other nicotinic acetylcholine receptors. J Neurosci. 1997 Nov 01; 17(21):8201-12. View in: PubMed

  58. Green WN, Wanamaker CP. The role of the cystine loop in acetylcholine receptor assembly. J Biol Chem. 1997 Aug 15; 272(33):20945-53. View in: PubMed

  59. Green WN, Claudio T. Acetylcholine receptor assembly: subunit folding and oligomerization occur sequentially. Cell. 1993 Jul 16; 74(1):57-69. View in: PubMed

  60. Jayawickreme SP, Green WN, Claudio T. Cyclic AMP-regulated AChR assembly is independent of AChR subunit phosphorylation by PKA. J Cell Sci. 1994 Jun; 107 ( Pt 6):1641-51. View in: PubMed

  61. Green WN, Millar NS. Ion-channel assembly. Trends Neurosci. 1995 Jun; 18(6):280-7. View in: PubMed

  62. Tam MR, Green WR, Nowinski RC. Cytotoxic activities of monoclonal antibodies against the envelope proteins of murine leukemia virus. Cancer Res. 1980 Oct; 40(10):3850-3. View in: PubMed

  63. Claudio T, Green WN, Hartman DS, Hayden D, Paulson HL, Sigworth FJ, Sine SM, Swedlund A. Genetic reconstitution of functional acetylcholine receptor channels in mouse fibroblasts. Science. 1987 Dec 18; 238(4834):1688-94. View in: PubMed

  64. Green WN, Andersen OS. Surface charges near the guanidinium neurotoxin binding site. Ann N Y Acad Sci. 1986; 479:306-12. View in: PubMed

  65. Claudio T, Paulson HL, Green WN, Ross AF, Hartman DS, Hayden D. Fibroblasts transfected with Torpedo acetylcholine receptor beta-, gamma-, and delta-subunit cDNAs express functional receptors when infected with a retroviral alpha recombinant. J Cell Biol. 1989 Jun; 108(6):2277-90. View in: PubMed

  66. Green WN, Weiss LB, Andersen OS. Batrachotoxin-modified sodium channels in planar lipid bilayers. Characterization of saxitoxin- and tetrodotoxin-induced channel closures. J Gen Physiol. 1987 Jun; 89(6):873-903. View in: PubMed

  67. Green WN, Weiss LB, Andersen OS. Batrachotoxin-modified sodium channels in planar lipid bilayers. Ion permeation and block. J Gen Physiol. 1987 Jun; 89(6):841-72. View in: PubMed

  68. Hartman DS, Poo MM, Green WN, Ross AF, Claudio T. Synaptic contact between embryonic neurons and acetylcholine receptor-fibroblast. J Physiol (Paris). 1990; 84(1):42-9. View in: PubMed

  69. Paulson HL, Ross AF, Green WN, Claudio T. Analysis of early events in acetylcholine receptor assembly. J Cell Biol. 1991 Jun; 113(6):1371-84. View in: PubMed

  70. Green WN, Ross AF, Claudio T. Acetylcholine receptor assembly is stimulated by phosphorylation of its gamma subunit. Neuron. 1991 Oct; 7(4):659-66. View in: PubMed

  71. Ross AF, Green WN, Hartman DS, Claudio T. Efficiency of acetylcholine receptor subunit assembly and its regulation by cAMP. J Cell Biol. 1991 May; 113(3):623-36. View in: PubMed

  72. Green WN, Ross AF, Claudio T. cAMP stimulation of acetylcholine receptor expression is mediated through posttranslational mechanisms. Proc Natl Acad Sci U S A. 1991 Feb 01; 88(3):854-8. View in: PubMed

  73. Green WN, Andersen OS. Surface charges and ion channel function. Annu Rev Physiol. 1991; 53:341-59. View in: PubMed

  74. Chabala LD, Urban BW, Weiss LB, Green WN, Andersen OS. Steady-state gating of batrachotoxin-modified sodium channels. Variability and electrolyte-dependent modulation. J Gen Physiol. 1991 Jul; 98(1):197-224. View in: PubMed

  75. Wong VG, Green WR, Liu YP, Marsden ER. Experimental intraocular malignancy: the effect of intracameral perfusion. Trans Am Ophthalmol Soc. 1979; 77:63-79. View in: PubMed