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 295 (5563): 2276-2279

Copyright © 2002 by the American Association for the Advancement of Science

Neuronal Calcium Sensor 1 and Activity-Dependent Facilitation of P/Q-Type Calcium Currents at Presynaptic Nerve Terminals

Tetsuhiro Tsujimoto,1*dagger Andreas Jeromin,2* Naoto Saitoh,1 John C. Roder,2 Tomoyuki Takahashi1

P/Q-type presynaptic calcium currents (IpCa) undergo activity-dependent facilitation during repetitive activation at the calyx of the Held synapse. We investigated whether neuronal calcium sensor 1 (NCS-1) may underlie this phenomenon. Direct loading of NCS-1 into the nerve terminal mimicked activity-dependent IpCa facilitation by accelerating the activation time of IpCa in a Ca2+-dependent manner. A presynaptically loaded carboxyl-terminal peptide of NCS-1 abolished IpCa facilitation. These results suggest that residual Ca2+ activates endogenous NCS-1, thereby facilitating IpCa. Because both P/Q-type Ca2+ channels and NCS-1 are widely expressed in mammalian nerve terminals, NCS-1 may contribute to the activity-dependent synaptic facilitation at many synapses.

1 Department of Neurophysiology, University of Tokyo Faculty of Medicine, Tokyo 113-0033, Japan.
2 Mount Sinai Hospital Research Institute, Toronto, Ontario M5G 1X5, Canada.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: tujimoto-tky{at}

Cav2.1 Channels Control Multivesicular Release by Relying on Their Distance from Exocytotic Ca2+ Sensors at Rat Cerebellar Granule Cells.
S. Satake and K. Imoto (2014)
J. Neurosci. 34, 1462-1474
   Abstract »    Full Text »    PDF »
Activity-Dependent Neurotrophin Signaling Underlies Developmental Switch of Ca2+ Channel Subtypes Mediating Neurotransmitter Release.
T. Miki, H. Hirai, and T. Takahashi (2013)
J. Neurosci. 33, 18755-18763
   Abstract »    Full Text »    PDF »
Calcium Channels and Short-term Synaptic Plasticity.
W. A. Catterall, K. Leal, and E. Nanou (2013)
J. Biol. Chem. 288, 10742-10749
   Abstract »    Full Text »    PDF »
Fine-tuning synaptic plasticity by modulation of CaV2.1 channels with Ca2+ sensor proteins.
K. Leal, S. Mochida, T. Scheuer, and W. A. Catterall (2012)
PNAS 109, 17069-17074
   Abstract »    Full Text »    PDF »
Molecular Determinants of Modulation of CaV2.1 Channels by Visinin-like Protein 2.
E. Nanou, G. Q. Martinez, T. Scheuer, and W. A. Catterall (2012)
J. Biol. Chem. 287, 504-513
   Abstract »    Full Text »    PDF »
Molecular Determinants of CaV2.1 Channel Regulation by Calcium-binding Protein-1.
A. P. Few, E. Nanou, T. Scheuer, and W. A. Catterall (2011)
J. Biol. Chem. 286, 41917-41923
   Abstract »    Full Text »    PDF »
Neuronal Calcium Sensor-1 Promotes Immature Heart Function and Hypertrophy by Enhancing Ca2+ Signals.
T. Y. Nakamura, A. Jeromin, K. Mikoshiba, and S. Wakabayashi (2011)
Circ. Res. 109, 512-523
   Abstract »    Full Text »    PDF »
Structure of a Ca2+-Myristoyl Switch Protein That Controls Activation of a Phosphatidylinositol 4-Kinase in Fission Yeast.
S. Lim, T. Strahl, J. Thorner, and J. B. Ames (2011)
J. Biol. Chem. 286, 12565-12577
   Abstract »    Full Text »    PDF »
Contribution of calcium-dependent facilitation to synaptic plasticity revealed by migraine mutations in the P/Q-type calcium channel.
P. J. Adams, R. L. Rungta, E. Garcia, A. M. J. M. van den Maagdenberg, B. A. MacVicar, and T. P. Snutch (2010)
PNAS 107, 18694-18699
   Abstract »    Full Text »    PDF »
Post-tetanic increase in the fast-releasing synaptic vesicle pool at the expense of the slowly releasing pool.
J. S. Lee, W.-K. Ho, and S.-H. Lee (2010)
J. Gen. Physiol. 136, 259-272
   Abstract »    Full Text »    PDF »
The Diversity of Calcium Sensor Proteins in the Regulation of Neuronal Function.
H. V. McCue, L. P. Haynes, and R. D. Burgoyne (2010)
Cold Spring Harb Perspect Biol 2, a004085
   Abstract »    Full Text »    PDF »
Neuronal Calcium Sensor-1 (Ncs1p) Is Up-regulated by Calcineurin to Promote Ca2+ Tolerance in Fission Yeast.
N. Hamasaki-Katagiri and J. B. Ames (2010)
J. Biol. Chem. 285, 4405-4414
   Abstract »    Full Text »    PDF »
Plasticity between Neuronal Pairs in Layer 4 of Visual Cortex Varies with Synapse State.
I. Saez and M. J. Friedlander (2009)
J. Neurosci. 29, 15286-15298
   Abstract »    Full Text »    PDF »
Frequenin/NCS-1 and the Ca2+-channel {alpha}1-subunit co-regulate synaptic transmission and nerve-terminal growth.
J. S. Dason, J. Romero-Pozuelo, L. Marin, B. G. Iyengar, M. K. Klose, A. Ferrus, and H. L. Atwood (2009)
J. Cell Sci. 122, 4109-4121
   Abstract »    Full Text »    PDF »
Mechanisms underlying short-term modulation of transmitter release by presynaptic depolarization.
T. Hori and T. Takahashi (2009)
J. Physiol. 587, 2987-3000
   Abstract »    Full Text »    PDF »
A limited contribution of Ca2+ current facilitation to paired-pulse facilitation of transmitter release at the rat calyx of Held.
M. Muller, F. Felmy, and R. Schneggenburger (2008)
J. Physiol. 586, 5503-5520
   Abstract »    Full Text »    PDF »
Interactions between multiple sources of short-term plasticity during evoked and spontaneous activity at the rat calyx of Held.
M. H. Hennig, M. Postlethwaite, I. D. Forsythe, and B. P. Graham (2008)
J. Physiol. 586, 3129-3146
   Abstract »    Full Text »    PDF »
Developmental changes in calcium/calmodulin-dependent inactivation of calcium currents at the rat calyx of Held.
T. Nakamura, T. Yamashita, N. Saitoh, and T. Takahashi (2008)
J. Physiol. 586, 2253-2261
   Abstract »    Full Text »    PDF »
Presynaptic Calcium Channel Localization and Calcium-Dependent Synaptic Vesicle Exocytosis Regulated by the Fuseless Protein.
A. A. Long, E. Kim, H.-T. Leung, E. Woodruff III, L. An, R. W. Doerge, W. L. Pak, and K. Broadie (2008)
J. Neurosci. 28, 3668-3682
   Abstract »    Full Text »    PDF »
Neuronal calcium sensor-1 modulation of optimal calcium level for neurite outgrowth.
K. Hui, G.-H. Fei, B. J. Saab, J. Su, J. C. Roder, and Z.-P. Feng (2007)
Development 134, 4479-4489
   Abstract »    Full Text »    PDF »
IL1-receptor accessory protein-like 1 (IL1RAPL1), a protein involved in cognitive functions, regulates N-type Ca2+-channel and neurite elongation.
F. Gambino, A. Pavlowsky, A. Begle, J.-L. Dupont, N. Bahi, R. Courjaret, R. Gardette, H. Hadjkacem, H. Skala, B. Poulain, et al. (2007)
PNAS 104, 9063-9068
   Abstract »    Full Text »    PDF »
The role of synaptotagmin I C2A calcium-binding domain in synaptic vesicle clustering during synapse formation.
P. Gardzinski, D. W. K. Lee, G.-H. Fei, K. Hui, G. J. Huang, H.-S. Sun, and Z.-P. Feng (2007)
J. Physiol. 581, 75-90
   Abstract »    Full Text »    PDF »
Altered frequency-dependent inactivation and steady-state inactivation of polyglutamine-expanded {alpha}1A in SCA6.
H. Chen and E. S. Piedras-Renteria (2007)
Am J Physiol Cell Physiol 292, C1078-C1086
   Abstract »    Full Text »    PDF »
Parvalbumin Is a Mobile Presynaptic Ca2+ Buffer in the Calyx of Held that Accelerates the Decay of Ca2+ and Short-Term Facilitation.
M. Muller, F. Felmy, B. Schwaller, and R. Schneggenburger (2007)
J. Neurosci. 27, 2261-2271
   Abstract »    Full Text »    PDF »
An Increase in Calcium Influx Contributes to Post-Tetanic Potentiation at the Rat Calyx of Held Synapse.
R. L. P. Habets and J. G. G. Borst (2006)
J Neurophysiol 96, 2868-2876
   Abstract »    Full Text »    PDF »
Switching of Ca2+-Dependent Inactivation of CaV1.3 Channels by Calcium Binding Proteins of Auditory Hair Cells..
P. S. Yang, B. A. Alseikhan, H. Hiel, L. Grant, M. X. Mori, W. Yang, P. A. Fuchs, and D. T. Yue (2006)
J. Neurosci. 26, 10677-10689
   Abstract »    Full Text »    PDF »
Functional Implication of Neuronal Calcium Sensor-1 and Phosphoinositol 4-Kinase-beta Interaction in Regulated Exocytosis of PC12 Cells.
J. de Barry, A. Janoshazi, J. L. Dupont, O. Procksch, S. Chasserot-Golaz, A. Jeromin, and N. Vitale (2006)
J. Biol. Chem. 281, 18098-18111
   Abstract »    Full Text »    PDF »
Novel role of neuronal Ca2+ sensor-1 as a survival factor up-regulated in injured neurons.
T. Y. Nakamura, A. Jeromin, G. Smith, H. Kurushima, H. Koga, Y. Nakabeppu, S. Wakabayashi, and J. Nabekura (2006)
J. Cell Biol. 172, 1081-1091
   Abstract »    Full Text »    PDF »
Presynaptic N-type and P/Q-type Ca2+ channels mediating synaptic transmission at the calyx of Held of mice.
T. Ishikawa, M. Kaneko, H.-S. Shin, and T. Takahashi (2005)
J. Physiol. 568, 199-209
   Abstract »    Full Text »    PDF »
Developmental Activation of Calmodulin-Dependent Facilitation of Cerebellar P-Type Ca2+ Current.
D. Chaudhuri, B. A. Alseikhan, S. Y. Chang, T. W. Soong, and D. T. Yue (2005)
J. Neurosci. 25, 8282-8294
   Abstract »    Full Text »    PDF »
Differential Regulation of CaV2.1 Channels by Calcium-Binding Protein 1 and Visinin-Like Protein-2 Requires N-Terminal Myristoylation.
A. P. Few, N. J. Lautermilch, R. E. Westenbroek, T. Scheuer, and W. A. Catterall (2005)
J. Neurosci. 25, 7071-7080
   Abstract »    Full Text »    PDF »
Neuronal calcium sensor-1 potentiates glucose-dependent exocytosis in pancreatic {beta} cells through activation of phosphatidylinositol 4-kinase {beta}.
J. Gromada, C. Bark, K. Smidt, A. M. Efanov, J. Janson, S. A. Mandic, D.-L. Webb, W. Zhang, B. Meister, A. Jeromin, et al. (2005)
PNAS 102, 10303-10308
   Abstract »    Full Text »    PDF »
Unique modulation of L-type Ca2+ channels by short auxiliary {beta}1d subunit present in cardiac muscle.
R. M. Cohen, J. D. Foell, R. C. Balijepalli, V. Shah, J. W. Hell, and T. J. Kamp (2005)
Am J Physiol Heart Circ Physiol 288, H2363-H2374
   Abstract »    Full Text »    PDF »
Functional Compensation of P/Q by N-Type Channels Blocks Short-Term Plasticity at the Calyx of Held Presynaptic Terminal.
C. G. Inchauspe, F. J. Martini, I. D. Forsythe, and O. D. Uchitel (2004)
J. Neurosci. 24, 10379-10383
   Abstract »    Full Text »    PDF »
N-terminal Myristoylation Regulates Calcium-induced Conformational Changes in Neuronal Calcium Sensor-1.
A. Jeromin, D. Muralidhar, M. N. Parameswaran, J. Roder, T. Fairwell, S. Scarlata, L. Dowal, S. M. Mustafi, K. V. R. Chary, and Y. Sharma (2004)
J. Biol. Chem. 279, 27158-27167
   Abstract »    Full Text »    PDF »
Ca2+-Binding Protein-1 Facilitates and Forms a Postsynaptic Complex with Cav1.2 (L-Type) Ca2+ Channels.
H. Zhou, S.-A. Kim, E. A. Kirk, A. L. Tippens, H. Sun, F. Haeseleer, and A. Lee (2004)
J. Neurosci. 24, 4698-4708
   Abstract »    Full Text »    PDF »
Identification of Residues That Determine the Absence of a Ca2+/Myristoyl Switch in Neuronal Calcium Sensor-1.
D. W. O'Callaghan and R. D. Burgoyne (2004)
J. Biol. Chem. 279, 14347-14354
   Abstract »    Full Text »    PDF »
Molecular determinants of Ca2+/calmodulin-dependent regulation of Cav2.1 channels.
A. Lee, H. Zhou, T. Scheuer, and W. A. Catterall (2003)
PNAS 100, 16059-16064
   Abstract »    Full Text »    PDF »
T. Strahl, B. Grafelmann, J. Dannenberg, J. Thorner, and O. Pongs (2003)
J. Biol. Chem. 278, 49589-49599
   Abstract »    Full Text »    PDF »
Adenosine A1 receptor-mediated presynaptic inhibition at the calyx of Held of immature rats.
M. Kimura, N. Saitoh, and T. Takahashi (2003)
J. Physiol. 553, 415-426
   Abstract »    Full Text »    PDF »
Dynamics and calcium sensitivity of the Ca2+/myristoyl switch protein hippocalcin in living cells.
D. W. O'Callaghan, A. V. Tepikin, and R. D. Burgoyne (2003)
J. Cell Biol. 163, 715-721
   Abstract »    Full Text »    PDF »
Developmental decrease in synaptic facilitation at the mouse hippocampal mossy fibre synapse.
F. Mori-Kawakami, K. Kobayashi, and T. Takahashi (2003)
J. Physiol. 553, 37-48
   Abstract »    Full Text »    PDF »
IL1 receptor accessory protein like, a protein involved in X-linked mental retardation, interacts with Neuronal Calcium Sensor-1 and regulates exocytosis.
N. Bahi, G. Friocourt, A. Carrie, M. E. Graham, J. L. Weiss, P. Chafey, F. Fauchereau, R. D. Burgoyne, and J. Chelly (2003)
Hum. Mol. Genet. 12, 1415-1425
   Abstract »    Full Text »    PDF »
Protein Kinase A Mediates Voltage-Dependent Facilitation of Ca2+ Current in Presynaptic Hair Cells in Hermissenda crassicornis.
C. T. Tamse, Y. Xu, H. Song, L. Nie, and E. N. Yamoah (2003)
J Neurophysiol 89, 1718-1726
   Abstract »    Full Text »    PDF »
Down-regulation of Voltage-gated Ca2+ Channels by Neuronal Calcium Sensor-1 Is beta Subunit-specific.
M. Rousset, T. Cens, S. Gavarini, A. Jeromin, and P. Charnet (2003)
J. Biol. Chem. 278, 7019-7026
   Abstract »    Full Text »    PDF »
Phosphatidylinositol 4-OH Kinase Is a Downstream Target of Neuronal Calcium Sensor-1 in Enhancing Exocytosis in Neuroendocrine Cells.
M. Rajebhosale, S. Greenwood, J. Vidugiriene, A. Jeromin, and S. Hilfiker (2003)
J. Biol. Chem. 278, 6075-6084
   Abstract »    Full Text »    PDF »
Kainate Receptor-Dependent Short-Term Plasticity of Presynaptic Ca2+ Influx at the Hippocampal Mossy Fiber Synapses.
H. Kamiya, S. Ozawa, and T. Manabe (2002)
J. Neurosci. 22, 9237-9243
   Abstract »    Full Text »    PDF »
Interaction with Neuronal Calcium Sensor NCS-1 Mediates Desensitization of the D2 Dopamine Receptor.
N. Kabbani, L. Negyessy, R. Lin, P. Goldman-Rakic, and R. Levenson (2002)
J. Neurosci. 22, 8476-8486
   Abstract »    Full Text »    PDF »
Mechanisms Underlying the Neuronal Calcium Sensor-1-evoked Enhancement of Exocytosis in PC12 Cells.
S. Koizumi, P. Rosa, G. B. Willars, R. A. J. Challiss, E. Taverna, M. Francolini, M. D. Bootman, P. Lipp, K. Inoue, J. Roder, et al. (2002)
J. Biol. Chem. 277, 30315-30324
   Abstract »    Full Text »    PDF »
Modulation of Kv4-encoded K+ Currents in the Mammalian Myocardium by Neuronal Calcium Sensor-1.
W. Guo, S. A. Malin, D. C. Johns, A. Jeromin, and J. M. Nerbonne (2002)
J. Biol. Chem. 277, 26436-26443
   Abstract »    Full Text »    PDF »
Activating calcium release through inositol 1,4,5-trisphosphate receptors without inositol 1,4,5-trisphosphate.
M. D. Bootman, M. J. Berridge, and H. L. Roderick (2002)
PNAS 99, 7320-7322
   Full Text »    PDF »

To Advertise     Find Products

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