The fully linked HTML version of this article has now been published.
JCS ePress
online publication date 28 Mar 2006
doi: 10.1242/jcs.02875
Research Article
NFATc1 nucleocytoplasmic shuttling is controlled by nerve activity in skeletal muscle
Jana Tothova,
Bert Blaauw,
Giorgia Pallafacchina,
Rüdiger Rudolf,
Carla Argentini,
Carlo Reggiani,
and
Stefano Schiaffino*
* Author for correspondence (e-mail: stefano.schiaffino{at}unipd.it)
Calcineurin-NFAT signaling has been shown to control activity-dependent muscle gene regulation and induce a program of gene expression typical of slow oxidative muscle fibers. Following Ca2+-calmodulin stimulation, calcineurin dephosphorylates NFAT proteins and induces their translocation into the nucleus. However, NFAT nuclear translocation has never been investigated in skeletal muscle in vivo. To determine whether NFATc1 nucleocytoplasmic shuttling depends on muscle activity, we transfected fast and slow mouse muscles with plasmids coding for an NFATc1-GFP fusion protein. We found that NFATc1-GFP has a predominantly cytoplasmic localization in the fast tibialis anterior muscle but a predominantly nuclear localization in the slow soleus muscle, with a characteristic focal intranuclear distribution. Two hours of complete inactivity, induced by denervation or anaesthesia, cause NFATc1 export out of the nucleus in soleus muscle fibers, whereas electrostimulation of tibialis anterior with a low-frequency tonic impulse pattern, mimicking the firing pattern of slow motor neurons, causes NFATc1 nuclear translocation. The activity-dependent nuclear import and export of NFATc1 is a rapid event, as visualized directly in vivo by two-photon microscopy. The calcineurin inhibitor cain/cabin1 causes nuclear export of NFATc1 both in normal soleus and stimulated tibialis anterior muscle. These findings support the notion that in skeletal muscle NFATc1 is a calcineurin-dependent nerve activity sensor.

CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati
Twitter What's this?
This article has been cited by other articles:

|
 |

|
 |
 
M. Murgia, T. E. Jensen, M. Cusinato, M. Garcia, E. A. Richter, and S. Schiaffino
Multiple signalling pathways redundantly control glucose transporter GLUT4 gene transcription in skeletal muscle
J. Physiol.,
September 1, 2009;
587(17):
4319 - 4327.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Calabria, S. Ciciliot, I. Moretti, M. Garcia, A. Picard, K. A. Dyar, G. Pallafacchina, J. Tothova, S. Schiaffino, and M. Murgia
NFAT isoforms control activity-dependent muscle fiber type specification
PNAS,
August 11, 2009;
106(32):
13335 - 13340.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
O. Agbulut, A. Vignaud, C. Hourde, E. Mouisel, F. Fougerousse, G. S. Butler-Browne, and A. Ferry
Slow myosin heavy chain expression in the absence of muscle activity
Am J Physiol Cell Physiol,
January 1, 2009;
296(1):
C205 - C214.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. W. Tsika, C. Schramm, G. Simmer, D. P. Fitzsimons, R. L. Moss, and J. Ji
Overexpression of TEAD-1 in Transgenic Mouse Striated Muscles Produces a Slower Skeletal Muscle Contractile Phenotype
J. Biol. Chem.,
December 26, 2008;
283(52):
36154 - 36167.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Z. A. Rana, K. Gundersen, and A. Buonanno
Activity-dependent repression of muscle genes by NFAT
PNAS,
April 15, 2008;
105(15):
5921 - 5926.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. A. Valdes, E. Gaggero, J. Hidalgo, N. Leal, E. Jaimovich, and M. A. Carrasco
NFAT activation by membrane potential follows a calcium pathway distinct from other activity-related transcription factors in skeletal muscle cells
Am J Physiol Cell Physiol,
March 1, 2008;
294(3):
C715 - C725.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. J. Rose, C. Frosig, B. Kiens, J. F. P. Wojtaszewski, and E. A. Richter
Effect of endurance exercise training on Ca2+ calmodulin-dependent protein kinase II expression and signalling in skeletal muscle of humans
J. Physiol.,
September 1, 2007;
583(2):
785 - 795.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Schiaffino, M. Sandri, and M. Murgia
Activity-Dependent Signaling Pathways Controlling Muscle Diversity and Plasticity
Physiology,
August 1, 2007;
22(4):
269 - 278.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. J. Rose, T. J. Alsted, J. B. Kobbero, and E. A. Richter
Regulation and function of Ca2+-calmodulin-dependent protein kinase II of fast-twitch rat skeletal muscle
J. Physiol.,
May 1, 2007;
580(3):
993 - 1005.
[Abstract]
[Full Text]
[PDF]
|
 |
|
© The Company of Biologists Ltd 2006