Error message

No crossref credentials set for sci

Requirement of Voltage-Gated Calcium Channel ß4 Subunit for T Lymphocyte Functions

Science, 7 January 2005
Vol. 307, Issue 5706, p. 117-121
DOI: 10.1126/science.1100582

Requirement of Voltage-Gated Calcium Channel ß4 Subunit for T Lymphocyte Functions

  1. Abdallah Badou1,
  2. Srisaila Basavappa2,4,
  3. Rooma Desai3,
  4. You-Qing Peng4,
  5. Didi Matza1,
  6. Wajahat Z. Mehal1,
  7. Leonard K. Kaczmarek2,3,
  8. Emile L. Boulpaep2,
  9. Richard A. Flavell1,*
  1. 1 Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
  2. 2 Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510, USA.
  3. 3 Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA.
  4. 4 Digestive Diseases Unit, Department of Medicine, Pharmacology and Physiology, University of Rochester School of Medicine.
  1. * To whom correspondence should be addressed. E-mail: richard.flavell{at}yale.edu

Abstract

Calcium is known to play vital roles in diverse physiological processes, and it is known that voltage-gated calcium channels (Cav) mediate calcium influx in excitable cells. However, no consensus exists on the molecular identity of the calcium channels present in nonexcitable cells such as T lymphocytes. Here, we demonstrate that T lymphocytes express both regulatory β4 and poreforming Cav1 α1 subunits of Cav channels. Cav β4-mutant T lymphocytes fail to acquire normal functions and display impairment in the calcium response, activation of the transcription factor NFAT, and cytokine production. Although Cav1 channels of lymphocytes retain their voltage dependency, T cell receptor stimulation dramatically increases channel opening, providing a new mechanism for calcium entry in lymphocytes.

  • Received for publication 21 May 2004.
  • Accepted for publication 23 November 2004.

Citation:

A. Badou, S. Basavappa, R. Desai, Y.-Q. Peng, D. Matza, W. Z. Mehal, L. K. Kaczmarek, E. L. Boulpaep, and R. A. Flavell, Requirement of Voltage-Gated Calcium Channel ß4 Subunit for T Lymphocyte Functions. Science 307, 117-121 (2005).

Genomic organization, expression, and phylogenetic analysis of Ca2+ channel {beta}4 genes in 13 vertebrate species
A. M. Ebert, C. A. McAnelly, A. V. Handschy, R. L. Mueller, W. A. Horne, and D. M. Garrity
Physiol. Genomics 35, 133-144 (8 October 2008)

Wogonin preferentially kills malignant lymphocytes and suppresses T-cell tumor growth by inducing PLC{gamma}1- and Ca2+-dependent apoptosis
S. Baumann, S. C. Fas, M. Giaisi, W. W. Muller, A. Merling, K. Gulow, L. Edler, P. H. Krammer, and M. Li-Weber
Blood 111, 2354-2363 (15 February 2008)

Critical role for the {beta} regulatory subunits of Cav channels in T lymphocyte function
A. Badou, M. K. Jha, D. Matza, W. Z. Mehal, M. Freichel, V. Flockerzi, and R. A. Flavell
Proc. Natl. Acad. Sci. USA 103, 15529-15534 (17 October 2006)

Retraction
R. A. Flavell, L. K. Kaczmarek, A. Badou, E. L. Boulpaep, R. Desai, S. Basavappa, D. Matza, Y.-Q. Peng, and W. Z. Mehal
Science 310, 1903b-1903b (23 December 2005)

A severe defect in CRAC Ca2+ channel activation and altered K+ channel gating in T cells from immunodeficient patients
S. Feske, M. Prakriya, A. Rao, and R. S. Lewis
JEM 202, 651-662 (6 September 2005)

Ca2+ Influx through L-type Ca2+ Channels Controls the Trailing Tail Contraction in Growth Factor-induced Fibroblast Cell Migration
S. Yang, and X.-Y. Huang
J Biol Chem 280, 27130-27137 (22 July 2005)

Highlights from the Literature
X.-Y. Huang
Physiology 20, 81-85 (1 April 2005)

IMMUNOLOGY: Decoding Calcium Signaling
M. M. Winslow, and G. R. Crabtree
Science 307, 56-57 (7 January 2005)

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