RETRACTED: Requirement of voltage-gated calcium channel beta4 subunit for T lymphocyte functions.
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 beta4 and poreforming Cav1 alpha1 subunits of Cav channels. Cav beta4-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.
Badou
Abdallah
A
Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
Basavappa
Srisaila
S
Desai
Rooma
R
Peng
You-Qing
YQ
Matza
Didi
D
Mehal
Wajahat Z
WZ
Kaczmarek
Leonard K
LK
Boulpaep
Emile L
EL
Flavell
Richard A
RA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D020013:Calcium Signaling; D016207:Cytokines / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000378:metabolism; D015640:Ion Channel Gating; D008213:Lymphocyte Activation; D008564:Membrane Potentials; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009154:Mutation; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D021122:Protein Subunits / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D020746:Calcium Channels, L-Type; D016207:Cytokines; D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D021122:Protein Subunits; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; D002118:Calcium