Selected Publications

Molecular motions of ion channels

• Liu L, Kohout SC, Xu Q, Muller S, Kimberlin CR, Isacoff EY, Minor DL Jr (2012). A glutamate switch controls voltage-sensitive phosphatase function. Nat Struct Mol Biol 19, 633-41.
• Reiner A, Arant RJ, Isacoff EY (2012). Assembly Stoichiometry of the GluK2/GluK5 Kainate Receptor Complex. Cell Reports 1, 234-40.
• Berger TK, Isacoff EY (2011). The pore of the voltage-gated proton channel. Neuron 72, 991-1000.
• Janovjak H, Sandoz G, Isacoff EY (2011). A modern ionotropic glutamate receptor with a K+ selectivity signature sequence. Nat Commun 2, 232.
• Sandoz G, Bell SC, Isacoff EY (2011). Optical probing of a dynamic membrane interaction that regulates the TREK1 channel. Proc Natl Acad Sci U S A 108, 2605-10.
• Kohout SC, Bell SC, Liu L, Xu Q, Minor DL Jr, Isacoff EY (2010). Electrochemical coupling in the voltage-dependent phosphatase ci-vsp. Nat Chem Biol 6, 369-75.
• Tombola F, Ulbrich MH, Kohout SC, Isacoff EY (2010). The opening of the two pores of the Hv1 voltage-gated proton channel is tuned by cooperativity. Nat Struct Mol Biol 17, 44-50.
• Kubo Y, Isacoff EY (2009). Dynamic aspects of functioning membrane proteins. J Physiol 587, 5315-6.
• Tombola F, Ulbrich MH, Isacoff EY (2009). Architecture and gating of Hv1 proton channels. J Physiol 587, 5325-9.
• Yu Y, Ulbrich MH, Li MH, Buraei Z, Chen XZ, Ong AC, Tong L, Isacoff, EY, Yang J (2009). Structural and molecular basis of the assembly of the trpp2/pkd1 complex. Proc Natl Acad Sci U S A 106, 11558-63.
• Martos V, Bell SC, Santos E, Isacoff EY, Trauner D, de Mendoza J (2009). Molecular recognition and self-assembly special feature: Calix[4]arene-based conical-shaped ligands for voltage-dependent potassium channels. Proc Natl Acad Sci U S A 106, 10482-6.
• Ulbrich MH, Isacoff EY (2008). Rules of engagement for NMDA receptor subunits. Proc Natl Acad Sci U S A 105, 14163-8.
• Tombola F, Ulbrich MH, Isacoff EY (2008). The voltage-gated proton channel Hv1 has two pores, each controlled by one voltage sensor. Neuron 58, 546-56.
• Kohout SC, Ulbrich MH, Bell SC, Isacoff EY (2008). Subunit organization and functional transitions in Ci-VSP. Nat Struct Mol Biol 15, 106-8.
• Pathak M, Yarov-Yarovoy V, Agarwal G, Roux B, Barth P, Kohout S, Tombola F, Isacoff EY (2007). Closing in on the resting state of the Shaker K(+) channel. Neuron 56, 124-40.
• Ulbrich MH, Isacoff EY (2007). Subunit counting in membrane-bound proteins. Nat Methods 4, 319-21.
• Tombola F, Pathak M, Gorostiza P, Isacoff EY (2007). The twisted ion-permeation pathway of a resting voltage-sensing domain. Nature 445, 546-9.
• Tombola F, Pathak M, Isacoff EY (2006). How does voltage open an ion channel? Annu Rev Cell Dev Biol 22, 23-52.
• Tombola F, Pathak M, Isacoff EY (2005). Voltage-sensing arginines in a potassium channel permeate and occlude cation-selective pores. Neuron 45, 379-88.
• Pathak M, Kurtz L, Tombola F, Isacoff EY (2005). A cooperative voltage sensor motion that gates a potassium channel. J Gen Physiol 125, 57-69.
• Gorostiza, P., Tombola, F., Verdaguer, A., Smith, S.B., Bustamante, C. and Isacoff, E.Y. (2005). Molecular Handles for the Mechanical Manipulation of Single-Membrane Proteins in Living Cells. IEEE Trans Nanobioscience 4, 269-76.
• Gandhi CS, Clark E, Loots E, Pralle A, Isacoff EY (2003). The orientation and molecular movement of a K+ channel voltage-sensing domain. Neuron 40, 515-25.
• Sonnleitner A, Mannuzzu LM, Terakawa S, Isacoff EY (2002). Structural rearrangements in single ion channels detected optically in living cells. Proc Natl Acad Sci U S A 99, 12759-64.
• Schonherr R, Mannuzzu LM, Isacoff EY, Heinemann SH (2002). Conformational switch between slow and fast gating modes: allosteric regulation of voltage sensor mobility in the EAG K+ channel. Neuron 35, 935-49.
• Gandhi CS, Loots E, Isacoff EY (2000). Reconstructing voltage sensor - pore interaction from a fluorescence scan of a voltage-gated K+ channel. Neuron 27, 585-95.
• Loots E, Isacoff EY (2000). Molecular coupling of voltage sensor to inactivation gate in the Shaker K+ channel. J Gen Physiol 116, 623-35.
• Mannuzzu LM, Isacoff EY (2000). Independence and cooperativity in rearrangements of a potassium channel voltage sensor revealed by single subunit fluorescence. J Gen Physiol 115, 257-68.
• Glauner KS, Mannuzzu LM, Gandhi CS, Isacoff EY (1999). Spectroscopic mapping of voltage sensor movement in the Shaker potassium channel. Nature 402, 813-7.

• Baker OS, Larsson HP, Mannuzzu LM, Isacoff EY (1998). Three transmembrane states and sequence-dependent displacement of the S4 domain in Shaker K+ channel gating. Neuron 20, 1283-94.
• Loots E, Isacoff, EY (1998). Protein rearrangements underlying slow inactivation of a K+ channel. J Gen Physiol 112, 377-89.

• Larsson HP, Baker OS, Dhillon DS, Isacoff EY (1996). Transmembrane movement of the Shaker K+ channel S4. Neuron 16, 387-97.

• Mannuzzu LM, Maronne MM, Isacoff EY (1996). Direct physical measure of conformational rearrangement underlying potassium channel gating. Science 271, 213-6.

Optical probes for detection and remote control of neural signaling

• Sandoz G, Levitz J, Kramer RH, Isacoff EY (2012). Optical Control of Endogenous Proteins with a Photoswitchable Conditional Subunit Reveals a Role for TREK1 in GABA(B) Signaling. Neuron 74, 1005-1014.
• Janovjak H, Szobota S, Wyart C, Trauner D, Isacoff EY (2010). A light-gated, potassium-selective glutamate receptor for the optical inhibition of neuronal firing. Nat Neurosci 13, 1027-32
• Siegel MS, Isacoff EY (2010). Green fluorescent proteins (GFPs) for measuring voltage. Cold Spring Harb Protoc 2010(4), pdb.top76.
• Szobota S, Isacoff EY (2010). Optical control of neuronal activity. Annu Rev Biophys 39, 329-48.
• Numano R, Szobota S, Lau AY, Gorostiza P, Volgraf M, Roux B, Trauner D, Isacoff EY (2009). Nanosculpting reversed wavelength sensitivity into a photoswitchable LiGluR. Proc Natl Acad Sci U S A 106, 6814-9.
• Wang S, Szobota S, Wang Y, Volgraf M, Liu Z, Sun C, Trauner D, Isacoff EY, Zhang X (2007). All optical interface for parallel, remote, and spatiotempoeral control of neuronal activity. Nano Lett 7, 3859-63.
• Gorostiza P, Volgraf M, Numano R, Szobota S, Trauner D, Isacoff EY (2007). Mechanisms of photoswitch conjugation and light activation of an ionotropic glutamate receptor. Proc Natl Acad Sci U S A 104, 10865-70.
• Szobota S, Gorostiza P, Del Bene F, Wyart C, Fortin DL, Kolstad KD, Tulyathan O, Volgraf M, Numano R, Aaron HL, Scott EK, Kramer RH, Baier H, Trauner D, Isacoff EY (2007). Remote control of neuronal activity with a light-gated glutamate receptor. Neuron 54, 535-45.
• Miller E, Tulyathan O, Isacoff EY, Chang CJ (2007). Molecular imaging of hydrogen peroxide produced for cell signaling. Nat Chem Biol 3, 263-7.

• Volgraf M, Gorostiza P, Szobota S, Helix MR, Isacoff EY, Trauner D. (2007). Reversibly caged glutamate: a photochromic agonist of ionotropic glutamate receptors. J Am Chem Soc 129, 260-1.
• Baker BJ, Lee H, Pieribone VA, Cohen LB, Isacoff EY, Knopfel T, Kosmidis EK (2007). Three fluorescent protein voltage sensors exhibit low plasma membrane expression in mammalian cells. J Neurosci Methods 161, 32-8.
• Volgraf M, Gorostiza P, Numano R, Kramer RH, Isacoff EY, Trauner, D. (2006). Allosteric Control of an Ionotropic Glutamate Receptor With an Optical Switch. Nat Chem Bio 2, 47-52.

• Kalab P, Pralle A, Isacoff EY, Heald R, Weis K. (2006). Analysis of a RanGTP-regulated gradient essential for mitosis in somatic cells. Nature 440, 697-701.

• Zeng L, Pralle A, Isacoff EY, Chang CJ (2006). A Selective Turn-On Fluorescent Sensor for Imaging Copper in Living Cells. J Am Chem Soc 128, 10-1.

• Miller EW, Albers AE, Pralle A, Isacoff EY, Chang CJ (2005). Boronate-based fluorescent probes for imaging cellular hydrogen peroxide. J Am Chem Soc 127, 16652-9.

• Cohen BE, Pralle A, Yao XJ, Swaminath G, Gandhi C, Jan YN, Kobilka BK, Isacoff EY, Jan LY (2005). A fluorescent probe designed for studying protein conformational change. Proc Natl Acad Sci U S A 102, 965-70.

• Reiff DF, Ihring A, Guerrero G, Isacoff EY, Joesch M, Nakai J, Borst A. (2005). In vivo performance of genetically encoded indicators of neural activity in flies. J Neurosci 25, 4766-78.

• Banghart M, Borges K, Isacoff EY, Trauner D, Kramer RH (2004). Light-activated ion channels for remote control of neuronal firing. Nat Neurosci 7, 1381-6.

• Chang MCY, Pralle A, Isacoff EY, Chang CY (2004). A Selective, Cell-Permeable Optical Probe for Hydrogen Peroxide in Living Cells. J Am Chem Soc 126, 15392-3.

• Gradl SN, Felix JP, Isacoff EY, Garcia ML, Trauner D. (2003) Protein Surface Recognition by Rational Design: Nanomolar Ligands for Potassium Channels. J Am Chem Soc 125, 12668-69.

• Guerrero G, Siegel MS, Roska B, Loots E, Isacoff EY (2002). Tuning FlaSh: Redesign of the dynamics, voltage range and color of the genetically-encoded optical sensor of membrane potential. Biophys J 83, 3607-18.

• Siegel MS, Isacoff EY (1997). A genetically encoded optical probe of membrane voltage. Neuron 19, 735-41

Synapse development

• Peled ES, Isacoff EY (2011). Optical quantal analysis of synaptic transmission in wild-type and rab3-mutant Drosophila motor axons. Nat Neurosci 14, 519-26.
• Agarwal G, Isacoff EY (2011). Specializations of a Pheromonal Glomerulus in the Drosophila Olfactory System. J Neurophysiol 105, 1711-21.
• Pautot S, Wyart C, Isacoff EY (2008). Colloid-guided assembly of oriented 3D neuronal networks. Nat Methods 5(8), 735-40.
• Stowers RS, Isacoff EY (2007). 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. J Neurosci 27, 12874-83.

• Guerrero G, Agarwal G, Reiff DF, Ball RW, Borst A, Goodman CS Isacoff EY (2005). Heterogeneity in synaptic transmission along a Drosophila larval motor axon. Nat Neurosci 8, 1188-96.

• Pautot S, Lee H, Isacoff EY, Groves JT (2005). Molecular adhesion of the neuronal synapse reconstituted between live cells and supported lipid bilayer. Nat Chem Bio 1, 283-9.

• Baksh MM, Dean C, Pautot S, DeMaria S, Isacoff E, Groves JT (2005). Neuronal Activation by GPI-linked Neuroligin-1 Displayed in Synthetic Lipid Bilayer Membranes. Langmuire 21, 10693-8.

• Dean C, Scholl FG, Choih J, Berger J, Isacoff EY, Scheiffele P (2003). Oligomeric Complexes of Neuroligin Mediate Synaptic Adhesion with Neurexin and Induce the Formation of Presynaptic Terminals. Nat Neurosci 6, 708-16.

• Zito K, Parnas D, Fetter RD, Isacoff EY, Goodman CS (1999). Live imaging of synaptic growth at the Drosophila neuromuscular junction. Neuron 22, 1-20

• Zito K, Fetter RD, Goodman CS, Isacoff EY (1997). Synaptic clustering of Fasciclin II and Shaker: Essential targeting sequences and role of DLG. Neuron 19, 1007-16.

In vivo circuit development and function in zebrafish

• Warp E, Agarwal G, Wyart C, Friedmann D, Oldfield CS, Conner A, Del Bene F, Arrenberg AB, Baier H, Isacoff EY (2012). Emergence of patterned activity in the developing zebrafish spinal cord. Curr Biol 22, 93-102.

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

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