Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 304 (5668): 265-270

Copyright © 2004 by the American Association for the Advancement of Science

Functional Conversion Between A-Type and Delayed Rectifier K+ Channels by Membrane Lipids

Dominik Oliver,1* Cheng-Chang Lien,1* Malle Soom,2 Thomas Baukrowitz,2 Peter Jonas,1{dagger} Bernd Fakler1{dagger}

Abstract: Voltage-gated potassium (Kv) channels control action potential repolarization, interspike membrane potential, and action potential frequency in excitable cells. It is thought that the combinatorial association between distinct {alpha} and ß subunits determines whether Kv channels function as non-inactivating delayed rectifiers or as rapidly inactivating A-type channels. We show that membrane lipids can convert A-type channels into delayed rectifiers and vice versa. Phosphoinositides remove N-type inactivation from A-type channels by immobilizing the inactivation domains. Conversely, arachidonic acid and its amide anandamide endow delayed rectifiers with rapid voltage-dependent inactivation. The bidirectional control of Kv channel gating by lipids may provide a mechanism for the dynamic regulation of electrical signaling in the nervous system.

1 Institute of Physiology, University of Freiburg, Hermann-Herder-Straße 7, 79104 Freiburg, Germany.
2 Institute of Physiology II, University of Jena, Teichgraben 8, 07744 Jena, Germany.

Back to Top

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: bernd.fakler{at} (B.F.) and peter.jonas{at} (P.J.)

Lipid Bilayer Modules as Determinants of K+ Channel Gating.
R. Syeda, J. S. Santos, and M. Montal (2014)
J. Biol. Chem. 289, 4233-4243
   Abstract »    Full Text »    PDF »
Dynamic PIP2 interactions with voltage sensor elements contribute to KCNQ2 channel gating.
Q. Zhang, P. Zhou, Z. Chen, M. Li, H. Jiang, Z. Gao, and H. Yang (2013)
PNAS 110, 20093-20098
   Abstract »    Full Text »    PDF »
Heme impairs the ball-and-chain inactivation of potassium channels.
N. Sahoo, N. Goradia, O. Ohlenschlager, R. Schonherr, M. Friedrich, W. Plass, R. Kappl, T. Hoshi, and S. H. Heinemann (2013)
PNAS 110, E4036-E4044
   Abstract »    Full Text »    PDF »
Regulation of Ion Channels by Pyridine Nucleotides.
P. J. Kilfoil, S. M. Tipparaju, O. A. Barski, and A. Bhatnagar (2013)
Circ. Res. 112, 721-741
   Abstract »    Full Text »    PDF »
Modulation of neuropathic-pain-related behaviour by the spinal endocannabinoid/endovanilloid system.
K. Starowicz and B. Przewlocka (2012)
Phil Trans R Soc B 367, 3286-3299
   Abstract »    Full Text »    PDF »
Dual Effect of Phosphatidyl (4,5)-Bisphosphate PIP2 on Shaker K+ Channels.
F. Abderemane-Ali, Z. Es-Salah-Lamoureux, L. Delemotte, M. A. Kasimova, A. J. Labro, D. J. Snyders, D. Fedida, M. Tarek, I. Baro, and G. Loussouarn (2012)
J. Biol. Chem. 287, 36158-36167
   Abstract »    Full Text »    PDF »
PIP2 controls voltage-sensor movement and pore opening of Kv channels through the S4-S5 linker.
A. A. Rodriguez-Menchaca, S. K. Adney, Q.-Y. Tang, X.-Y. Meng, A. Rosenhouse-Dantsker, M. Cui, and D. E. Logothetis (2012)
PNAS 109, E2399-E2408
   Abstract »    Full Text »    PDF »
Fitting KV potassium channels into the PIP2 puzzle: Hille group connects dots between illustrious HH groups.
D. W. Hilgemann (2012)
J. Gen. Physiol. 140, 245-248
   Full Text »    PDF »
Regulation of voltage-gated potassium channels by PI(4,5)P2.
M. Kruse, G. R. V. Hammond, and B. Hille (2012)
J. Gen. Physiol. 140, 189-205
   Abstract »    Full Text »    PDF »
Ca2+/cAMP-Sensitive Covariation of IA and IH Voltage Dependences Tunes Rebound Firing in Dopaminergic Neurons.
J. Amendola, A. Woodhouse, M.-F. Martin-Eauclaire, and J.-M. Goaillard (2012)
J. Neurosci. 32, 2166-2181
   Abstract »    Full Text »    PDF »
Modulation of Kv3.4 channel N-type inactivation by protein kinase C shapes the action potential in dorsal root ganglion neurons.
D. M. Ritter, C. Ho, M. E. O'Leary, and M. Covarrubias (2012)
J. Physiol. 590, 145-161
   Abstract »    Full Text »    PDF »
Voltage-Gated Potassium Currents Are Targets of Diurnal Changes in Estradiol Feedback Regulation and Kisspeptin Action on Gonadotropin-Releasing Hormone Neurons in Mice.
J. Pielecka-Fortuna, R. A. DeFazio, and S. M. Moenter (2011)
Biol Reprod 85, 987-995
   Abstract »    Full Text »    PDF »
Deficiency in the Omega-3 Fatty Acid Pathway Results in Failure of Acrosome Biogenesis in Mice.
M. Roqueta-Rivera, T. L. Abbott, M. Sivaguru, R. A. Hess, and M. T. Nakamura (2011)
Biol Reprod 85, 721-732
   Abstract »    Full Text »    PDF »
The pore structure and gating mechanism of K2P channels.
P. L. Piechotta, M. Rapedius, P. J. Stansfeld, M. K. Bollepalli, G. Erhlich, I. Andres-Enguix, H. Fritzenschaft, N. Decher, M. S. P. Sansom, S. J. Tucker, et al. (2011)
EMBO J. 30, 3607-3619
   Abstract »    Full Text »    PDF »
Probing the regulation of TASK potassium channels by PI(4,5)P2 with switchable phosphoinositide phosphatases.
M. Lindner, M. G. Leitner, C. R. Halaszovich, G. R. V. Hammond, and D. Oliver (2011)
J. Physiol. 589, 3149-3162
   Abstract »    Full Text »    PDF »
Coupling of the phosphatase activity of Ci-VSP to its voltage sensor activity over the entire range of voltage sensitivity.
S. Sakata, M. I. Hossain, and Y. Okamura (2011)
J. Physiol. 589, 2687-2705
   Abstract »    Full Text »    PDF »
KCNE1 enhances phosphatidylinositol 4,5-bisphosphate (PIP2) sensitivity of IKs to modulate channel activity.
Y. Li, M. A. Zaydman, D. Wu, J. Shi, M. Guan, B. Virgin-Downey, and J. Cui (2011)
PNAS 108, 9095-9100
   Abstract »    Full Text »    PDF »
Oxidation of NADPH on Kv{beta}1 inhibits ball-and-chain type inactivation by restraining the chain.
Y. Pan, J. Weng, E. J. Levin, and M. Zhou (2011)
PNAS 108, 5885-5890
   Abstract »    Full Text »    PDF »
Plasticity in Membrane Cholesterol Contributes toward Electrical Maturation of Hearing.
S. Levic and E. N. Yamoah (2011)
J. Biol. Chem. 286, 5768-5773
   Abstract »    Full Text »    PDF »
Aminoglycosides Inhibit KCNQ4 Channels in Cochlear Outer Hair Cells via Depletion of Phosphatidylinositol(4,5)bisphosphate.
M. G. Leitner, C. R. Halaszovich, and D. Oliver (2011)
Mol. Pharmacol. 79, 51-60
   Abstract »    Full Text »    PDF »
International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid Receptors and Their Ligands: Beyond CB1 and CB2.
R. G. Pertwee, A. C. Howlett, M. E. Abood, S. P. H. Alexander, V. Di Marzo, M. R. Elphick, P. J. Greasley, H. S. Hansen, G. Kunos, K. Mackie, et al. (2010)
Pharmacol. Rev. 62, 588-631
   Abstract »    Full Text »    PDF »
Channels get in an HUFA: RNA editing gets them out of a jam.
R. Horn and R. Reenan (2010)
EMBO J. 29, 2097-2098
   Abstract »    Full Text »    PDF »
RNA editing modulates the binding of drugs and highly unsaturated fatty acids to the open pore of Kv potassium channels.
N. Decher, A. K. Streit, M. Rapedius, M. F. Netter, S. Marzian, P. Ehling, G. Schlichthorl, T. Craan, V. Renigunta, A. Kohler, et al. (2010)
EMBO J. 29, 2101-2113
   Abstract »    Full Text »    PDF »
Molecular Basis for a High-Potency Open-Channel Block of Kv1.5 Channel by the Endocannabinoid Anandamide.
E. G. Moreno-Galindo, G. F. Barrio-Echavarria, J. C. Vasquez, N. Decher, F. B. Sachse, M. Tristani-Firouzi, J. A. Sanchez-Chapula, and R. A. Navarro-Polanco (2010)
Mol. Pharmacol. 77, 751-758
   Abstract »    Full Text »    PDF »
Ancillary Subunits Associated With Voltage-Dependent K+ Channels.
O. Pongs and J. R. Schwarz (2010)
Physiol Rev 90, 755-796
   Abstract »    Full Text »    PDF »
Endocannabinoids and cannabinoid analogues block cardiac hKv1.5 channels in a cannabinoid receptor-independent manner.
A. Barana, I. Amoros, R. Caballero, R. Gomez, L. Osuna, M. P. Lillo, C. Blazquez, M. Guzman, E. Delpon, and J. Tamargo (2010)
Cardiovasc Res 85, 56-67
   Abstract »    Full Text »    PDF »
The Ca2+ channel {beta} subunit determines whether stimulation of Gq-coupled receptors enhances or inhibits N current.
J. F. Heneghan, T. Mitra-Ganguli, L. F. Stanish, L. Liu, R. Zhao, and A. R. Rittenhouse (2009)
J. Gen. Physiol. 134, 369-384
   Abstract »    Full Text »    PDF »
An oily competition: role of {beta} subunit palmitoylation for Ca2+ channel modulation by fatty acids.
J. Striessnig (2009)
J. Gen. Physiol. 134, 363-367
   Full Text »    PDF »
Cholesterol modulates the recruitment of Kv1.5 channels from Rab11-associated recycling endosome in native atrial myocytes.
E. Balse, S. El-Haou, G. Dillanian, A. Dauphin, J. Eldstrom, D. Fedida, A. Coulombe, and S. N. Hatem (2009)
PNAS 106, 14681-14686
   Abstract »    Full Text »    PDF »
Hyperpolarization-Activated Cation Channels: From Genes to Function.
M. Biel, C. Wahl-Schott, S. Michalakis, and X. Zong (2009)
Physiol Rev 89, 847-885
   Abstract »    Full Text »    PDF »
Inhibition of Kv1.3 potassium current by phosphoinositides and stromal-derived factor-1{alpha} in Jurkat T cells.
Y. Matsushita, S. Ohya, Y. Suzuki, H. Itoda, T. Kimura, H. Yamamura, and Y. Imaizumi (2009)
Am J Physiol Cell Physiol 296, C1079-C1085
   Abstract »    Full Text »    PDF »
Inhibitory effects of polyunsaturated fatty acids on Kv4/KChIP potassium channels.
L. M. Boland, M. M. Drzewiecki, G. Timoney, and E. Casey (2009)
Am J Physiol Cell Physiol 296, C1003-C1014
   Abstract »    Full Text »    PDF »
Phosphoinositide signalling and cardiac arrhythmias.
E. A. Woodcock, P. M. Kistler, and Y.-K. Ju (2009)
Cardiovasc Res 82, 286-295
   Abstract »    Full Text »    PDF »
Arachidonic acid inhibition of L-type calcium (CaV1.3b) channels varies with accessory CaV{beta} subunits.
M. L. Roberts-Crowley and A. R. Rittenhouse (2009)
J. Gen. Physiol. 133, 387-403
   Abstract »    Full Text »    PDF »
Structural Insights into KChIP4a Modulation of Kv4.3 Inactivation.
P. Liang, H. Wang, H. Chen, Y. Cui, L. Gu, J. Chai, and K. Wang (2009)
J. Biol. Chem. 284, 4960-4967
   Abstract »    Full Text »    PDF »
Resynthesis of phosphatidylinositol 4,5-bisphosphate mediates adaptation of the caffeine response in rat taste receptor cells.
F.-l. Zhao and S. Herness (2009)
J. Physiol. 587, 363-377
   Abstract »    Full Text »    PDF »
The Endogenous Brain Constituent N-Arachidonoyl L-Serine Is an Activator of Large Conductance Ca2+-Activated K+ Channels.
G. Godlewski, L. Offertaler, D. Osei-Hyiaman, F. M. Mo, J. Harvey-White, J. Liu, M. I. Davis, L. Zhang, R. K. Razdan, G. Milman, et al. (2009)
J. Pharmacol. Exp. Ther. 328, 351-361
   Abstract »    Full Text »    PDF »
Voltage-dependent K+ channel gating and voltage sensor toxin sensitivity depend on the mechanical state of the lipid membrane.
D. Schmidt and R. MacKinnon (2008)
PNAS 105, 19276-19281
   Abstract »    Full Text »    PDF »
Structural determinants of Kv{beta}1.3-induced channel inactivation: a hairpin modulated by PIP2.
N. Decher, T. Gonzalez, A. K. Streit, F. B. Sachse, V. Renigunta, M. Soom, S. H. Heinemann, J. Daut, and M. C. Sanguinetti (2008)
EMBO J. 27, 3164-3174
   Abstract »    Full Text »    PDF »
Phosphoinositides Suppress {gamma}-Secretase in Both the Detergent-soluble and -insoluble States.
S. Osawa, S. Funamoto, M. Nobuhara, S. Wada-Kakuda, M. Shimojo, S. Yagishita, and Y. Ihara (2008)
J. Biol. Chem. 283, 19283-19292
   Abstract »    Full Text »    PDF »
PIP2 PIP2 Hooray for Maxi K+.
A. R. Rittenhouse (2008)
J. Gen. Physiol. 132, 5-8
   Full Text »    PDF »
Amino Acid Substitutions in the Pore Helix of GluR6 Control Inhibition by Membrane Fatty Acids.
T. J. Wilding, E. Fulling, Y. Zhou, and J. E. Huettner (2008)
J. Gen. Physiol. 132, 85-99
   Abstract »    Full Text »    PDF »
Physiology and Pathophysiology of Potassium Channels in Gastrointestinal Epithelia.
D. Heitzmann and R. Warth (2008)
Physiol Rev 88, 1119-1182
   Abstract »    Full Text »    PDF »
Arachidonic Acid Activates Kir2.3 Channels by Enhancing Channel-Phosphatidyl-inositol 4,5-bisphosphate Interactions.
C. Wang, U. L. Mirshahi, B. Liu, Z. Jia, T. Mirshahi, and H. Zhang (2008)
Mol. Pharmacol. 73, 1185-1194
   Abstract »    Full Text »    PDF »
The Endogenous Cannabinoid Anandamide Inhibits Cromakalim-Activated K+ Currents in Follicle-Enclosed Xenopus Oocytes.
M. Oz, K.-H. Yang, M. Dinc, and T. S. Shippenberg (2007)
J. Pharmacol. Exp. Ther. 323, 547-554
   Abstract »    Full Text »    PDF »
The Endocannabinoid Anandamide Inhibits the Function of {alpha}4beta2 Nicotinic Acetylcholine Receptors.
C. E. Spivak, C. R. Lupica, and M. Oz (2007)
Mol. Pharmacol. 72, 1024-1032
   Abstract »    Full Text »    PDF »
Molecular Determinants of PI(4,5)P2 and PI(3,4,5)P3 Regulation of the Epithelial Na+ Channel.
O. Pochynyuk, Q. Tong, J. Medina, A. Vandewalle, A. Staruschenko, V. Bugaj, and J. D. Stockand (2007)
J. Gen. Physiol. 130, 399-413
   Abstract »    Full Text »    PDF »
Depolarization activates the phosphoinositide phosphatase Ci-VSP, as detected in Xenopus oocytes coexpressing sensors of PIP2.
Y. Murata and Y. Okamura (2007)
J. Physiol. 583, 875-889
   Abstract »    Full Text »    PDF »
Membrane cholesterol modulates Kv1.5 potassium channel distribution and function in rat cardiomyocytes.
J. Abi-Char, A. Maguy, A. Coulombe, E. Balse, P. Ratajczak, J.-L. Samuel, S. Nattel, and S. N. Hatem (2007)
J. Physiol. 582, 1205-1217
   Abstract »    Full Text »    PDF »
S-acylation regulates Kv1.5 channel surface expression.
L. Zhang, K. Foster, Q. Li, and J. R. Martens (2007)
Am J Physiol Cell Physiol 293, C152-C161
   Abstract »    Full Text »    PDF »
A New Mode of Regulation of N-type Inactivation in a Caenorhabditis elegans Voltage-gated Potassium Channel.
S.-Q. Cai and F. Sesti (2007)
J. Biol. Chem. 282, 18597-18601
   Abstract »    Full Text »    PDF »
Receptor-specific inhibition of GABAB-activated K+ currents by muscarinic and metabotropic glutamate receptors in immature rat hippocampus.
J.-W. Sohn, D. Lee, H. Cho, W. Lim, H.-S. Shin, S.-H. Lee, and W.-K. Ho (2007)
J. Physiol. 580, 411-422
   Abstract »    Full Text »    PDF »
Alteration of Epithelial Structure and Function Associated with PtdIns(4,5)P2 Degradation by a Bacterial Phosphatase.
D. Mason, G. V. Mallo, M. R. Terebiznik, B. Payrastre, B. B. Finlay, J. H. Brumell, L. Rameh, and S. Grinstein (2007)
J. Gen. Physiol. 129, 267-283
   Abstract »    Full Text »    PDF »
HCN Pacemaker Channel Activation Is Controlled by Acidic Lipids Downstream of Diacylglycerol Kinase and Phospholipase A2.
K. J. Fogle, A. K. Lyashchenko, H. K. Turbendian, and G. R. Tibbs (2007)
J. Neurosci. 27, 2802-2814
   Abstract »    Full Text »    PDF »
Modulation of the Pancreatic Islet beta-Cell-delayed Rectifier Potassium Channel Kv2.1 by the Polyunsaturated Fatty Acid Arachidonate.
D. A. Jacobson, C. R. Weber, S. Bao, J. Turk, and L. H. Philipson (2007)
J. Biol. Chem. 282, 7442-7449
   Abstract »    Full Text »    PDF »
Chemical Determinants Involved in Anandamide-induced Inhibition of T-type Calcium Channels.
J. Chemin, J. Nargeot, and P. Lory (2007)
J. Biol. Chem. 282, 2314-2323
   Abstract »    Full Text »    PDF »
Voltage Gating of VDAC Is Regulated by Nonlamellar Lipids of Mitochondrial Membranes.
T. K. Rostovtseva, N. Kazemi, M. Weinrich, and S. M. Bezrukov (2006)
J. Biol. Chem. 281, 37496-37506
   Abstract »    Full Text »    PDF »
M1 Muscarinic Receptors Inhibit L-type Ca2+ Current and M-Current by Divergent Signal Transduction Cascades..
L. Liu, R. Zhao, Y. Bai, L. F. Stanish, J. E. Evans, M. J. Sanderson, J. V. Bonventre, and A. R. Rittenhouse (2006)
J. Neurosci. 26, 11588-11598
   Abstract »    Full Text »    PDF »
Ca2+ influx through CRAC channels activates cytosolic phospholipase A2, leukotriene C4 secretion, and expression of c-fos through ERK-dependent and -independent pathways in mast cells.
W.-C. Chang, C. Nelson, and A. B. Parekh (2006)
FASEB J 20, 2381-2383
   Abstract »    Full Text »    PDF »
Interplay between PIP3 and calmodulin regulation of olfactory cyclic nucleotide-gated channels.
J. D. Brady, E. D. Rich, J. R. Martens, J. W. Karpen, M. D. Varnum, and R. L. Brown (2006)
PNAS 103, 15635-15640
   Abstract »    Full Text »    PDF »
Regulation of the desensitization and ion selectivity of ATP-gated P2X2 channels by phosphoinositides.
Y. Fujiwara and Y. Kubo (2006)
J. Physiol. 576, 135-149
   Abstract »    Full Text »    PDF »
Effect of an unstirred layer on the membrane permeability of anandamide.
I. N. Bojesen and H. S. Hansen (2006)
J. Lipid Res. 47, 561-570
   Abstract »    Full Text »    PDF »
{Delta}9-Tetrahydrocannabinol and Endogenous Cannabinoid Anandamide Directly Potentiate the Function of Glycine Receptors.
N. Hejazi, C. Zhou, M. Oz, H. Sun, J. H. Ye, and L. Zhang (2006)
Mol. Pharmacol. 69, 991-997
   Abstract »    Full Text »    PDF »
Acceleration of K+ channel inactivation by MEK inhibitor U0126.
L.-L. Yuan, X. Chen, K. Kunjilwar, P. Pfaffinger, and D. Johnston (2006)
Am J Physiol Cell Physiol 290, C165-C171
   Abstract »    Full Text »    PDF »
{omega}-3 and {omega}-6 polyunsaturated fatty acids block HERG channels.
M. Guizy, C. Arias, M. David, T. Gonzalez, and C. Valenzuela (2005)
Am J Physiol Cell Physiol 289, C1251-C1260
   Abstract »    Full Text »    PDF »
PIP2 Activates TRPV5 and Releases Its Inhibition by Intracellular Mg2+.
J. Lee, S.-K. Cha, T.-J. Sun, and C.-L. Huang (2005)
J. Gen. Physiol. 126, 439-451
   Abstract »    Full Text »    PDF »
Direct Modulation of Kir Channel Gating by Membrane Phosphatidylinositol 4,5-Bisphosphate.
D. Enkvetchakul, I. Jeliazkova, and C. G. Nichols (2005)
J. Biol. Chem. 280, 35785-35788
   Abstract »    Full Text »    PDF »
Q/R Site Editing Controls Kainate Receptor Inhibition by Membrane Fatty Acids.
T. J. Wilding, Y. Zhou, and J. E. Huettner (2005)
J. Neurosci. 25, 9470-9478
   Abstract »    Full Text »    PDF »
Biophysical and pharmacological properties of the voltage-gated potassium current of human pancreatic {beta}-cells.
J. Herrington, M. Sanchez, D. Wunderler, L. Yan, R. M Bugianesi, I. E Dick, S. A Clark, R. M Brochu, B. T Priest, M. G Kohler, et al. (2005)
J. Physiol. 567, 159-175
   Abstract »    Full Text »    PDF »
Mutations in the Arabidopsis Phosphoinositide Phosphatase Gene SAC9 Lead to Overaccumulation of PtdIns(4,5)P2 and Constitutive Expression of the Stress-Response Pathway.
M. E. Williams, J. Torabinejad, E. Cohick, K. Parker, E. J. Drake, J. E. Thompson, M. Hortter, and D. B. DeWald (2005)
Plant Physiology 138, 686-700
   Abstract »    Full Text »    PDF »
A phospholipid sensor controls mechanogating of the K+ channel TREK-1.
J. Chemin, A. J. Patel, F. Duprat, I. Lauritzen, M. Lazdunski, and E. Honore (2005)
EMBO J. 24, 44-53
   Abstract »    Full Text »    PDF »
Phosphotidylinositol 4,5-Bisphosphate Signals Underlie Receptor-Specific Gq/11-Mediated Modulation of N-Type Ca2+ Channels.
N. Gamper, V. Reznikov, Y. Yamada, J. Yang, and M. S. Shapiro (2004)
J. Neurosci. 24, 10980-10992
   Abstract »    Full Text »    PDF »
Functional coupling of intracellular calcium and inactivation of voltage-gated Kv1.1/Kv{beta}1.1 A-type K+ channels.
F. Jow, Z.-H. Zhang, D. C. Kopsco, K. C. Carroll, and K. Wang (2004)
PNAS 101, 15535-15540
   Abstract »    Full Text »    PDF »
Switching desaturase enzyme specificity by alternate subcellular targeting.
I. Heilmann, M. S. Pidkowich, T. Girke, and J. Shanklin (2004)
PNAS 101, 10266-10271
   Abstract »    Full Text »    PDF »
BIOCHEMISTRY: Oily Barbarians Breach Ion Channel Gates.
D. W. Hilgemann (2004)
Science 304, 223-224
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882