Selected Publications

2016

Chen, Y., Bharril, S., Altun, Z., O'Hagan, R., Coblitz, B., Isacoff, E.Y., Chalfie, M. Caenorhabditis elegans paraoxonase-like proteins control the functional expression of DEG/ENaC mechanosensory proteins. Molecular Biology of the Cell (2016).

Grimm, S.S., Isacoff, E.Y. Allosteric substrate switching in a voltage-sensing lipid phosphatase. Nature Chemical Biology (2016).

Levitz, J., Royal, P., Comoglio, Y., Wdziekonski, B., Schaub, S., Clemens, D.M., Isacoff, E.Y., Sandoz, G. Heterodimerization within the TREK channel subfamily produces a diverse family of highly regulated potassium channels. PNAS (2016).

Huang, Y., Bharill, S., Karandur, D., Peterson, S.M., Marita, M., Shi, X., Kaliszewski, M.J., Smith, A.W., Isacoff, E.Y., Kuriyan, J. Molecular basis for multimerization in the activation of the epidermal growth factor receptor. eLife (2016).

Berlin, S., Szobota, S., Reiner, A., Carroll, E.C., Kienzler, M.A., Guyon, A., Xiao, T., Trauner, D., Isacoff, E.Y. A family of photoswitchable NMDA receptors. eLife (2016).

Levitz, J., Popescu, A.T., Reiner, A., Isacoff, E.Y. A Toolkit for orthogonal and in vivo optical manipulation of ionotropic glutamate receptors. Frontiers in Molecular Neuroscience (2016).

2015

Palty, R., Isacoff, E.Y. Cooperative Binding of Stromal Interaction Molecule 1 (STIM1) to the N and C Termini of Calcium Release-Activated Calcium Modulator 1 (Orai1). Journal of biological chemistry (2015).

Chen, Y., Bharill, S., Isacoff, E.Y., Chalfie, M. Subunit composition of a DEG/ENaC mechanosensory channel of Caenorhabditis elegans. PNAS (2015).

Vafabakhsh, R., Levitz, J., Isacoff, E.Y. Conformational dynamics of a class C G-protein-coupled receptor. Nature (2015).

Berlin, S., Carroll, E.C., Newman, Z.L., Okada, H.O., Quinn, C.M., Kallman, B., Rockwell, N.C., Martin, S.S., Lagarias, J.C., Isacoff, E.Y. Photoactivatable genetically encoded calcium indicators for targeted neuronal imaging. Nature Methods (2015).

Palty, R., Stanley, C., Isacoff, E.Y. Critical role for Orai1 C-terminal domain and TM4 in CRAC channel gating. Cell Research (2015).

Gaub, B.M., Berry, M.H., Holt, A.E., Isacoff, E.Y., Flannery, J.G. Optogenetic vision restoration using rhodopsin for enhanced sensitivity. Molecular Therapy (2015).

Ball, R.W., Peled, E.S., Guerrero, G., Isacoff, E.Y. BMP signaling and microtubule organization regulate synaptic strength Neuroscience (2015).

Mony, L., Berger, T.K., Isacoff, E.Y. A specialized molecular motion opens the Hv1 voltage-gated proton channel. Nature Structural & Molecular Biology 22, 283-90 (2015).

Carroll, E.C., Berlin, S., Levitz, J., Kienzler, M.A., Yuan, Z., Madsen, D., Larsen, D.S., Isacoff, E.Y. Two-photon brightness of azobenzene photoswitches designed for glutamate receptor optogenetics. PNAS 112, E776-85 (2015).

Reiner, A., Levitz, J., Isacoff, E.Y. Controlling ionotropic and metabotropic glutamate receptors with light: principles and potential. Current opinion in pharmacology 20, 135-43 (2015).

Berger, T.K., Isacoff, E.Y. Fluorescent labeling for patch-clamp fluorometry (PCF) measurements of real-time protein motion in ion channels. Methods in molecular biology 1266, 93-106 (2015).

Friedmann, D., Hoagland, A., Berlin, S., Isacoff, E.Y. A spinal opsin controls early neural activity and drives a behavioral light response. Current Biology 25, 69-74 (2015).

2014

Gaub, B.M., Berry, M.H., Holt, A.E., Reiner, A., Kienzler, M.A., Dolgova, N., Nikonov, S., Aguirre, G.D., Beltran, W.A., Flannery, J.G., Isacoff, E.Y. Restoration of visual function by expression of a light-gated mammalian ion channel in retinal ganglion cells or ON-bipolar cells. PNAS 111, E5574-83 (2014).

Comoglio, Y., Levitz, J., Kienzler, M.A., Lesage, F., Isacoff, E.Y., Sandoz, G. Phospholipase D2 specifically regulates TREK potassium channels via direct interaction and local production of phosphatidic acid. PNAS 111, 13547-52 (2014).

Fogel, H., Frere, S., Segev, O., Bharill, S., Shapira, I., Gazit, N., O'Malley, T., Slomowitz, E., Berdichevsky, Y., Walsh, D.M., Isacoff, E.Y., Hirsch, J.A., Slutsky, I. APP homodimers transduce an amyloid-beta-mediated increase in release probability at excitatory synapses. Cell Reports 7, 1560-76 (2014).

Bharill, S., Fu, Z., Palty, R., Isacoff, E.Y. Stoichiometry and specific assembly of Best ion channels. PNAS 111, 6491-6.

Reiner, A., Isacoff, E.Y. Photoswitching of cell surface receptors using tethered ligands. Methods in molecular biology 1148, 45-68 (2014).

Reiner, A., Isacoff, E.Y. Tethered ligands reveal glutamate receptor desensitization depends on subunit occupancy. Nature Chemical Biology 10, 273-80 (2014).

Peled, E.S., Newman, Z.L., Isacoff, E.Y. Evoked and spontaneous transmission favored by distinct sets of synapses. Current Biology 24, 484-93 (2014).

2013

Kienzler, M.A., Reiner, A., Trautman, E., Yoo, S., Trauner, D., Isacoff, E.Y. A red-shifted, fast-relaxing azobenzene photoswitch for visible light control of an ionotropic glutamate receptor. JACS 135, 17683-6 (2013).

Patti, J., Isacoff, E.Y. Measuring membrane voltage with fluorescent proteins. CSH Protocols (2013).

Kauwe, G., Isacoff, E.Y. Rapid feedback regulation of synaptic efficacy during high-frequency activity at the Drosophila larval neuromuscular junction. PNAS 110, 9142-7 (2013).

Hastie, P., Ulbrich, M.H., Wang, H.L., Arant, R.J., Lau, A.G., Zhang, Z., Isacoff, E.Y., Chen, L. AMPA receptor/TARP stoichiometry visualized by single-molecule subunit counting. PNAS 110, 5163-8 (2013).

Levitz, J., Pantoja, C., Gaub, B.M., Janovjak, H., Reiner, A., Hoagland, A., Schoppik, D., Kane, B., Stawski, P., Schier, A.F., Trauner, D., Isacoff, E.Y. Optical control of metabotropic glutamate receptors. Nature Neuroscience 16, 507-16 (2013).

2012

Yu, Y., Ulbrich, M.H., Li, M.H., Dobbins, S., Zhang, W.K., Tong, L., Isacoff, E.Y., Yang, J. Molecular mechanism of the assembly of an acid-sensing receptor ion channel complex. Nature Communications 3, 1252 (2012).

Sandoz, G., Levitz, J., Kramer, R.H., Isacoff, E.Y. Optical control of endogenous proteins with a photoswitchable conditional subunit reveals a role for TREK1 in GABA(B) signaling. Neuron 74, 1005-14 (2012).

Liu, L., Kohout, S., Xu, Q., Muller, S., Kimberlin, C.R., Isacoff, E.Y., Minor, D.L. Jr. A glutamate switch controls voltage-sensitive phosphatase function. Nature Structural & Molecular Biology 19, 633-41 (2012).

Reiner, A., Arant, R.J., Isacoff, E.Y. Assembly stoichiometry of the GluK2/GluK5 kainate receptor complex. Cell Reports 1, 234-40 (2012).

2011

Warp, E., Agarwal, G., Wyart, C., Friedmann, D., Oldfield, C., Conner, A., Del Bene, F., Arrenberg, A.B., Baier, H., Isacoff, E.Y. Emergence of patterned activity in the developing zebrafish spinal cord. Current Biology 22, 93-102 (2011).

Berger, T.K., Isacoff, E.Y. The pore of the voltage-gated proton channel. Neuron 72, 991-1000 (2011).

Caporale, N., Kolstad, K.D., Lee, T., Tochitsky, I., Dalkara, D., Trauner, D., Kramer, R.H., Dan, Y., Isacoff, E.Y., Flannery, J.G. LiGluR restores visual responses in rodent models of inherited blindness. Molecular Therapy 19, 1212-9 (2011).

Peled, E.S., Isacoff, E.Y. Optical quantal analysis of synaptic transmission in wild-type and rab3-mutant Drosophila motor axons. Nature Neuroscience 14, 519-26 (2011).

Agarwal, G., Isacoff, E.Y. Specializations of a pheromonal glomerulus in the Drosophila olfactory system. Journal of neurophysiology 105, 1711-21 (2011).

Sandoz, G., Bell, S.C., Isacoff, E.Y. Optical probing of a dynamic membrane interaction that regulates the TREK1 channel. PNAS 108, 2605-10 (2011).

2010

Del Bene, F., Wyart, C., Robles, E., Tran, A., Looger, L., Scott, E.K., Isacoff, E.Y., Baier, H. Filtering of visual information in the tectum by an identified neural circuit. Science 330, 669-73 (2010).

Nakajo, K., Ulbrich, M.H., Kubo, Y., Isacoff, E.Y. Stoichiometry of the KCNQ1 - KCNE1 ion channel complex. PNAS 107, 18751-2 (2010).

Kim, E.Y., Rumpf, C.H., Van Petegem, F., Arant, R.J., Findeisen, F., Cooley, E.S., Isacoff, E.Y., Minor, D.L. Jr. Multiple C-terminal tail Ca(2+)/CaMs regulate Ca(V)1.2 function but do not mediate channel dimerization. EMBO Journal 29, 3924-38 (2010).

Hanson, L., Dean, C., Isacoff, E. Alternative splicing of neuroglin regulates the rate of presynaptic differentiation. The Journal of Neuroscience 30, 11435-46 (2010).

Szobota, S., Wyart, C., Trauner, D., Isacoff, E.Y. A light-gated, potassium-selective glutamate receptor for the optical inhibition of neuronal firing. Nature Neuroscience 13, 1027-32 (2010).

Kohout, S.C., Bell, S.C., Liu, L., Xu, Q., Minor, D.L. Jr., Isacoff, E.Y. Electrochemical coupling in the voltage-dependent phosphatase Ci-VSP. Nature Chemical Biology 6, 369-75 (2010).

Siegel, M.S., Isacoff, E.Y. Green fluorescent proteins (GFPs) for measuring voltage. CSH Protocols (2010).

Szobota, S., Isacoff, E.Y. Optical control of neuronal activity. Annual review of biophysics 39, 329-48 (2010).

Tombola, F., Ulbrich, M.H., Kohout, S.C., Isacoff, E.Y. The opening of the two pores of the Hv1 voltage-gated proton channel is tuned by cooperativity. Nature Structural & Molecular Biology 17, 44-50 (2010).

2009

Tombola, F., Ulbrich, M.H., Isacoff, E.Y. Architecture and gating of Hv1 proton channels. The Journal of Physiology 587, 5325-9 (2009).

Wyart, C., Del Bene, F., Warp, E., Scott, E.K., Trauner, D., Baier, H., Isacoff, E.Y. Optogenetic dissection of a behavioural module in the vertebrate spinal cord. Nature 461, 407-10 (2009).

Yu, Y., Ulbrich, M.H., Li, M.H., Buraei, Z., Chen, X.Z., Ong, A.C., Tong, L., Isacoff, E.Y., Yang, J. Structural and molecular basis of the assembly of the TRPP2/PKD1 complex. PNAS 106, 11558-63 (2009).

Numano, R., Szobota, S., Lau, A.Y., Gorostiza, P., Volgraf, M., Roux, B., Trauner, D., Isacoff, E.Y. Nanosculpting reversed wavelength sensitivity into a photoswitchable iGluR. PNAS 106, 6814-9 (2009).

2008

Ulbrich, M.H., Isacoff, E.Y. Rules of engagement for NMDA receptor subunits. PNAS 105, 14163-8 (2008).

Pautot, S., Wyart, C., Isacoff, E.Y. Colloid-guided assembly of oriented 3D neuronal networks. Nature Methods 5, 735-40 (2008).

Tombola, F., Ulbrich, M.H., Isacoff, E.Y. The voltage-gated proton channel Hv1 has two pores, each controlled by one voltage sensor. Neuron 58, 546-56 (2008).

Kohout, S.C., Ulbrich, M.H., Bell, S.C., Isacoff, E.Y. Subunit organization and functional transitions in Ci-VSP. Nature Structural & Molecular Biology 15, 106-8 (2008).

2007

Wang, S., Szobota, S., Wang, Y., Volgraf, M., Liu, Z., Sun, C., Trauner, D., Isacoff, E.Y., Zhang, X. All optical interface for parallel, remote, and spatiotemporal control of neuronal activity. Nano Letters 7, 3859-63 (2007).

Stowers, R.S., Isacoff, E.Y. Drosophila huntingtin-interacting protein 14 is a presynaptic protein required for photoreceptor synaptic transmission and expression of the palmitoylated proteins synaptosome-associated protein 25 and cysteine string protein. The Journal of Neuroscience 27, 12874-83 (2007).

Pathak, M.M., Yarov-Yarovoy, V., Agarwal, G., Roux, B., Barth, P., Kohout, S.C., Tombola, F., Isacoff, E.Y. Closing in on the resting state of the Shaker K(+) channel. Neuron 56, 124-40 (2007).

Gorostiza, P., Volgraf, M., Numano, R., Szobota, S., Trauner, D., Isacoff, E.Y. Mechanisms of photoswitch conjugation and light activation of an ionotropic glutamate receptor. PNAS 104, 10865-70 (2007).

Szobota, S., Gorostiza, P., Del Bene, F., Wyart, C., Fortin, D.L., Kolstad, K.D., Tulyathan, O., Volgraf, M., Numano, R., Aaron, H.L., Scott, E.K., Kramer, R.H., Flannery, J.G., Baier, H., Trauner, D., Isacoff, E.Y. Remote control of neuronal activity with a light-gated glutamate receptor. Neuron 54, 535-45 (2007).

Miller, E.W., Tulyathan, O., Isacoff, E.Y., Chang, C.J. Molecular imaging of hydrogen peroxide produced for cell signaling. Nature Chemical Biology 3, 263-7 (2007).

Ulbrich, M.H., Isacoff, E.Y. Subunit counting in membrane-bound proteins. Nature Methods 4, 319-21 (2007).

Volgraf, M., Gorostiza, P., Szobota, S., Helix, M.R., Isacoff, E.Y., Trauner, D. Reversibly caged glutamate: a photochromic agonist of ionotropic glutamate receptors. JACS 129, 260-1 (2007).

Tombola, F., Pathak, M.M., Gorostiza, P., Isacoff, E.Y. The twisted ion-permeation pathway of a resting voltage-sensing domain. Nature 445, 546-9 (2007).

2006

Kalab, P., Pralle, A., Isacoff, E.Y., Heald, R., Weis, K. Analysis of a RanGTP-regulated gradient in mitotic somatic cells. Nature 440, 697-701 (2006).

Zeng, L., Miller, E.W., Chang, C.J. A selective turn-on fluorescent sensor for imaging copper in living cells. JACS 128, 10-1 (2006).

Volgraf, M., Gorostiza, P., Numano, R., Kramer, R.H., Isacoff, E.Y., Trauner, D. Allosteric control of an ionotropic glutamate receptor with an optical switch Nature Chemical Biology 2, 47-52 (2005).

2005

Gorostiza, P., Tombola, F., Verdaguer, A., Smith, S.B., Bustamante, C., Isacoff, E.Y. Molecular handles for the mechanical manipulation of single-membrane proteins in living cells. IEEE Transactions on Nanobioscience 4, 269-76 (2005).

Miller, E.W., Albers, A.E., Pralle, A., Isacoff, E.Y., Chang, C.J. Boronate-based fluorescent probes for imaging cellular hydrogen peroxide. JACS 127, 16652-9.

Guerrero, G., Reiff, D.F., Agarwal, G., Ball, R.W., Borst, A., Goodman, C.S., Isacoff, E.Y. Heterogeneity in synaptic transmission along a Drosophila larval motor axon. Nature Neuroscience 8, 1188-96 (2005).

Tombola, F., Pathak, M.M., Isacoff, E.Y. Voltage-sensing arginines in a potassium channel permeate and occlude cation-selective pores. Neuron 45, 379-88 (2005).

Reiff, D.F., Ihring, A., Guerrero, G., Isacoff, E.Y., Joesch, M., Nakai, J., Borst, A. In vivo performance of genetically encoded indicators of neural activity in flies. The Journal of Neuroscience 25, 4766-78 (2005).

Cohen, B.E., Pralle, A., Yao, X., Swaminath, G., Gandhi, C.S., Jan, Y.N., Kobilka, B.K., Isacoff, E.Y., Jan, L.Y. A fluorescent probe designed for studying protein conformational change. PNAS 102, 965-70 (2005).

Pathak, M.M., Kurtz, L., Tombola, F., Isacoff, E.Y. The cooperative voltage sensor motion that gates a potassium channel. The Journal of General Physiology 125, 57-69 (2005).

2004

Banghart, M., Borges, K., Isacoff, E.Y., Trauner, D., Kramer, R.H. Light-activated ion channels for remote control of neuronal firing. Nature Neuroscience 7, 1381-86 (2004).

Chang, M.C., Pralle, A., Isacoff, E.Y., Chang, C.J. A selective, cell-permeable optical probe for hydrogen peroxide in living cells. JACS 126, 15392-3 (2004).

2003

Gandhi, C.S., Clark, E., Loots, E., Pralle, A., Isacoff, E.Y. The orientation and molecular movement of a k(+) channel voltage-sensing domain. Neuron 40, 515-25 (2003).

Gradl, S.N., Felix, J.P., Isacoff, E.Y., Garcia, M.L., Trauner, D. Protein surface recognition by rational design: nanomolar ligands for potassium channels. JACS 125, 12668-9 (2003).

Dean, C., Scholl, F.G., Choih, J., DeMaria, S., Berger, J., Isacoff, E.Y., Scheiffele, P. Neurexin mediates the assembly of presynaptic terminals Nature Neuroscience 6, 708-16 (2003).

2002

Guerrero, G., Siegel, M.S., Roska, B., Loots, E., Isacoff, E.Y. Tuning FlaSh: redesign of the dynamics, voltage range, and color of the genetically encoded optical sensor of membrane potential. Biophysical Journal 83, 3607-18 (2002).

Schonherr, R., Mannuzzu, L.M., Isacoff, E.Y., Heinemann, S.H. Conformational switch between slow and fast gating modes: allosteric regulation of voltage sensor mobility in the EAG K+ channel. Neuron 35, 935-49 (2002).

Sonnleitner, A., Mannuzzu, L.M., Terakawa, S., Isacoff, E.Y. Structural rearrangements in single ion channels detected optically in living cells. PNAS 99, 12759-64 (2002).

2000 & Earlier

Loots, E., Isacoff, E.Y. Molecular coupling of S4 to a K(+) channel's slow inactivation gate. The Journal of General Physiology 116, 623-36 (2000).

Gandhi, C.S., Loots, E., Isacoff, E.Y. Reconstructing voltage sensor-pore interaction from a fluorescence scan of a voltage-gated K+ channel. Neuron 27, 585-95 (2000).

Siegel, M.S., Isacoff, E.Y. Green fluorescent protein-based sensors for detecting signal transduction and monitoring ion channel function. Methods in Enzymology 327, 249-59 (2000).

Mannuzzu, L.M., Isacoff, E.Y. Independence and cooperativity in rearrangements of a potassium channel voltage sensor revealed by single subunit fluorescence. The Journal of General Physiology 115, 257-68 (2000).

Glauner, K.S., Mannuzzu, L.M., Gandhi, C.S., Isacoff, E.Y. Spectroscopic mapping of voltage sensor movement in the Shaker potassium channel. Nature 402, 813-7 (1999).

Zito, K., Parnas, D., Fetter, R.D., Isacoff, E.Y., Goodman, C.S. Watching a synapse grow: noninvasive confocal imaging of synaptic growth in Drosophila. Neuron 22, 719-29 (1999).

Loots, E., Isacoff, E.Y. Protein rearrangements underlying slow inactivation of the Shaker K+ channel. The Journal of General Physiology 112, 377-89 (1998).

Baker, O.S., Larsson, H.P., Mannuzzu, L.M., Isacoff, E.Y. Three transmembrane conformations and sequence-dependent displacement of the S4 domain in shaker K+ channel gating. Neuron 20, 1283-94 (1998).

Zito, K., Fetter, R.D., Goodman, C.S., Isacoff, E.Y. Synaptic clustering of Fascilin II and Shaker: essential targeting sequences and role of Dlg. Neuron 19, 1007-16 (1997).

Siegel, M.S., Isacoff, E.Y. A genetically encoded optical probe of membrane voltage. Neuron 19, 735-41 (1997).

Harris, R.E., Isacoff, E.Y. Hydrophobic mutations alter the movement of Mg2+ in the pore of voltage-gated potassium channels. Biophysical Journal 71, 209-19 (1996).

Larsson, H.P., Baker, O.S., Dhillon, D.S., Isacoff, E.Y. Transmembrane movement of the shaker K+ channel S4. Neuron 16, 387-97 (1996).

Mannuzzu, L.M., Moronne, M.N., Isacoff, E.Y. Direct physical measure of conformational rearrangement underlying potassium channel gating. Science 271, 213-6 (1996).

Isacoff, E.Y., Jan, Y.N., Jan, L.Y. Putative receptor for the cytoplasmic inactivation gate in the Shaker K+ channel. Nature 353, 86-90 (1991).

Isacoff, E.Y., Jan, Y.N., Jan, L.Y. Evidence for the formation of heteromultimeric potassium channels in Xenopus oocytes. Nature 345, 530-4 (1990).

Birks, R.I., Isacoff, E.Y. Burst-patterned stimulation promotes nicotinic transmission in isolated perfused rat sympathetic ganglia The Journal of Physiology 402, 515-32 (1988).